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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 28 Mar 2024 at 01:56 Created: 

Mitochondrial Evolution

The endosymbiotic hypothesis for the origin of mitochondria (and chloroplasts) suggests that mitochondria are descended from specialized bacteria (probably purple nonsulfur bacteria) that somehow survived endocytosis by another species of prokaryote or some other cell type, and became incorporated into the cytoplasm.

Created with PubMed® Query: ( mitochondria AND evolution NOT 26799652[PMID] NOT 33634751[PMID] NOT 38225003[PMID]) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2024-03-26

Krasovec G, Horkan HR, Quéinnec É, et al (2024)

Intrinsic apoptosis is evolutionarily divergent among metazoans.

Evolution letters, 8(2):267-282.

Apoptosis is regulated cell death that depends on caspases. A specific initiator caspase is involved upstream of each apoptotic signaling pathway. Characterized in nematode, fly, and mammals, intrinsic apoptosis is considered to be ancestral, conserved among animals, and depends on shared initiators: caspase-9, Apaf-1 and Bcl-2. However, the biochemical role of mitochondria, the pivotal function of cytochrome c and the modality of caspase activation remain highly heterogeneous and hide profound molecular divergence among apoptotic pathways in animals. Uncovering the phylogenetic history of apoptotic actors, especially caspases, is crucial to shed light on the evolutionary history of intrinsic apoptosis. Here, we demonstrate with phylogenetic analyses that caspase-9, the fundamental key of intrinsic apoptosis, is deuterostome-specific, while caspase-2 is ancestral to bilaterians. Our analysis of Bcl-2 and Apaf-1 confirms heterogeneity in functional organization of apoptotic pathways in animals. Our results support emergence of distinct intrinsic apoptotic pathways during metazoan evolution.

RevDate: 2024-03-23
CmpDate: 2024-03-21

Duran DP, Laroche RA, Roman SJ, et al (2024)

Species delimitation, discovery and conservation in a tiger beetle species complex despite discordant genetic data.

Scientific reports, 14(1):6617.

In an age of species declines, delineating and discovering biodiversity is critical for both taxonomic accuracy and conservation. In recent years, there has been a movement away from using exclusively morphological characters to delineate and describe taxa and an increase in the use of molecular markers to describe diversity or through integrative taxonomy, which employs traditional morphological characters, as well as genetic or other data. Tiger beetles are charismatic, of conservation concern, and much work has been done on the morphological delineation of species and subspecies, but few of these taxa have been tested with genetic analyses. In this study, we tested morphologically based taxonomic hypotheses of polymorphic tiger beetles in the Eunota circumpicta (LaFerté-Sénectère, 1841) species complex using multilocus genomic and mtDNA analyses. We find multiple cryptic species within the previous taxonomic concept of Eunota circumpicta, some of which were historically recognized as subspecies. We found that the mtDNA and genomic datasets did not identify the same taxonomic units and that the mtDNA was most at odds with all other genetic and morphological patterns. Overall, we describe new cryptic diversity, which raises important conservation concerns, and provide a working example for testing species and subspecies validity despite discordant data.

RevDate: 2024-03-22
CmpDate: 2024-03-22

Liu T, Ji D, Li X, et al (2024)

Population genetics reveals new introgression in the nucleus herd of min pigs.

Genes & genomics, 46(4):389-398.

OBJECTIVE: Min pigs are a unique genetic resource among local pig breeds in China. They have more excellent characteristics in cold and stress resistance, good meat quality, and a high reproductive rate. However, the genetic structure and driving factors remain unclear in the nucleus herd. In this study, the genetic diversity of Min pigs was studied to reveal the formation mechanism of its unique genetic structure. We hope to protect and develop the genetic resources of Min pigs.

METHODS: We analyzed different types of genes to identify the genetic structure and gene introgression pattern of Min pigs. The nuclear DNA dataset includes information on 21 microsatellite loci and 6 Y-chromosome genes, and the mitochondrial D-loop gene is selected to represent maternal lineages. The above genes are all from the nucleus herd of Min pigs.

RESULTS: The results of genetic structure identification and analysis of potential exogenous gene introgression patterns indicate that the nucleus herd of Min pigs maintains a high level of genetic diversity (polymorphism information content = 0.713, expected heterozygosity = 0.662, observed heterozygosity = 0.612). Compared with other Asian pig breeds, the formation of Min pig breeds is more special. Gene introgression from European pig breeds to Min pigs has occurred, which is characterized by complete introgression of paternal genes and incomplete introgression of maternal genes.

CONCLUSION: Gene introgression caused by cross-breeding is not the main factor leading to the formation of the current genetic structure of Min pigs, but this process has increased the level of genetic diversity in the nucleus herd. Compared with the influence of gene introgression, our research suggest that artificial selection and environmental adaptive evolution make Min pigs form unique genetic characteristics.

RevDate: 2024-03-21
CmpDate: 2024-03-21

Nuryadi H, Mandagi IF, Masengi KWA, et al (2024)

Evidence for hybridization-driven heteroplasmy maintained across generations in a ricefish endemic to a Wallacean ancient lake.

Biology letters, 20(3):20230385.

Heteroplasmy, the presence of multiple mitochondrial DNA (mtDNA) haplotypes within cells of an individual, is caused by mutation or paternal leakage. However, heteroplasmy is usually resolved to homoplasmy within a few generations because of germ-line bottlenecks; therefore, instances of heteroplasmy are limited in nature. Here, we report heteroplasmy in the ricefish species Oryzias matanensis, endemic to Lake Matano, an ancient lake in Sulawesi Island, in which one individual was known to have many heterozygous sites in the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene. In this study, we cloned the ND2 gene for some additional individuals with heterozygous sites and demonstrated that they are truly heteroplasmic. Phylogenetic analysis revealed that the extra haplotype within the heteroplasmic O. matanensis individuals clustered with haplotypes of O. marmoratus, a congeneric species inhabiting adjacent lakes. This indicated that the heteroplasmy originated from paternal leakage due to interspecific hybridization. The extra haplotype was unique and contained two non-synonymous substitutions. These findings demonstrate that this hybridization-driven heteroplasmy was maintained across generations for a long time to the extent that the extra mitochondria evolved within the new host.

RevDate: 2024-03-21
CmpDate: 2024-03-21

Kuntz M, Dimnet L, Pullara S, et al (2024)

The Main Functions of Plastids.

Methods in molecular biology (Clifton, N.J.), 2776:89-106.

Plastids are semi-autonomous organelles like mitochondria and derive from a cyanobacterial ancestor that was engulfed by a host cell. During evolution, they have recruited proteins originating from the nuclear genome, and only parts of their ancestral metabolic properties were conserved and optimized to limit functional redundancy with other cell compartments. Furthermore, large disparities in metabolic functions exist among various types of plastids, and the characterization of their various metabolic properties is far from being accomplished. In this review, we provide an overview of the main functions, known to be achieved by plastids or shared by plastids and other compartments of the cell. In short, plastids appear at the heart of all main plant functions.

RevDate: 2024-03-19

Maréchal E (2024)

How Did Thylakoids Emerge in Cyanobacteria, and How Were the Primary Chloroplast and Chromatophore Acquired?.

Methods in molecular biology (Clifton, N.J.), 2776:3-20.

The emergence of thylakoid membranes in cyanobacteria is a key event in the evolution of all oxygenic photosynthetic cells, from prokaryotes to eukaryotes. Recent analyses show that they could originate from a unique lipid phase transition rather than from a supposed vesicular budding mechanism. Emergence of thylakoids coincided with the great oxygenation event, more than two billion years ago. The acquisition of semi-autonomous organelles, such as the mitochondrion, the chloroplast, and, more recently, the chromatophore, is a critical step in the evolution of eukaryotes. They resulted from primary endosymbiotic events that seem to share general features, i.e., an acquisition of a bacterium/cyanobacteria likely via a phagocytic membrane, a genome reduction coinciding with an escape of genes from the organelle to the nucleus, and, finally, the appearance of an active system translocating nuclear-encoded proteins back to the organelles. An intense mobilization of foreign genes of bacterial origin, via horizontal gene transfers, plays a critical role. Some third partners, like Chlamydia, might have facilitated the transition from cyanobacteria to the early chloroplast. This chapter further details our current understanding of primary endosymbiosis, focusing on primary chloroplasts, thought to have appeared over a billion years ago, and the chromatophore, which appeared around a hundred years ago.

RevDate: 2024-03-19

Yang Y, C Duan (2024)

Mitochondrial genome features and systematic evolution of diospyros kaki thunb 'Taishuu'.

BMC genomics, 25(1):285.

BACKGROUND: 'Taishuu' has a crisp texture, abundant juice, and sweet flavor with hints of cantaloupe. The availability of mitochondrial genome data of Diospyros species is far from the known number of species.

RESULTS: The sequencing data were assembled into a closed circular mitochondrial chromosome with a 421,308 bp length and a 45.79% GC content. The mitochondrial genome comprised 40 protein-coding, 24 tRNA, and three rRNA genes. The most common codons for arginine (Arg), proline (Pro), glycine (Gly), tryptophan (Trp), valine (Val), alanine (Ala), and leucine (Leu) were AGA, CCA, GGA, UGG, GUA, GCA, and CUA, respectively. The start codon for cox1 and nad4L protein-coding genes was ACG (ATG), whereas the remaining protein-coding genes started with ATG. There are four types of stop codons: CGA, TAA, TAG, and TGA, with TAA being the most frequently used stop codon (45.24%). In the D. kaki Thunb. 'Taishuu' mitochondrial genome, a total of 645 repeat sequences were identified, including 125 SSRs, 7 tandem repeats, and 513 dispersed repeats. Collinearity analysis revealed a close relationship between D. kaki Thunb. 'Taishuu' and Diospyros oleifera, with conserved homologous gene fragments shared among these species in large regions of the mitochondrial genome. The protein-coding genes ccmB and nad4L were observed to undergo positive selection. Analysis of homologous sequences between chloroplasts and mitochondria identified 28 homologous segments, with a total length of 24,075 bp, accounting for 5.71% of the mitochondrial genome. These homologous segments contain 8 annotated genes, including 6 tRNA genes and 2 protein-coding genes (rrn18 and ccmC). There are 23 homologous genes between chloroplasts and nuclei. Mitochondria, chloroplasts, and nuclei share two homologous genes, which are trnV-GAC and trnW-CCA.

CONCLUSION: In conclusion, a high-quality chromosome-level draft genome for D. kaki was generated in this study, which will contribute to further studies of major economic traits in the genus Diospyros.

RevDate: 2024-03-16

Keeling PJ, Mtawali M, Trznadel M, et al (2024)

Parallel functional reduction in the mitochondria of apicomplexan parasites.

European journal of protistology, 94:126065 pii:S0932-4739(24)00015-4 [Epub ahead of print].

Extreme functional reduction of mitochondria has taken place in parallel in many distantly related lineages of eukaryotes, leading to a number of recurring metabolic states with variously lost electron transport chain (ETC) complexes, loss of the tricarboxylic acid (TCA) cycle, and/or loss of the mitochondrial genome. The resulting mitochondria-related organelles (MROs) are generally structurally reduced and in the most extreme cases barely recognizable features of the cell with no role in energy metabolism whatsoever (e.g., mitosomes, which generally only make iron-sulfur clusters). Recently, a wide diversity of MROs were discovered to be hiding in plain sight: in gregarine apicomplexans. This diverse group of invertebrate parasites has been known and observed for centuries, but until recent applications of culture-free genomics, their mitochondria were unremarkable. The genomics, however, showed that mitochondrial function has reduced in parallel in multiple gregarine lineages to several different endpoints, including the most reduced mitosomes. Here we review this remarkable case of parallel evolution of MROs, and some of the interesting questions this work raises.

RevDate: 2024-03-18
CmpDate: 2024-03-18

Li CY, Liu XC, Li YZ, et al (2024)

Generation of mitochondrial replacement monkeys by female pronucleus transfer.

Zoological research, 45(2):292-298.

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys (Macaca fascicularis) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

RevDate: 2024-03-15

Na I, Campos C, Lax G, et al (2024)

Phylogenomics reveals Adeleorina are an ancient and distinct subgroup of Apicomplexa.

Molecular phylogenetics and evolution, 195:108060 pii:S1055-7903(24)00052-6 [Epub ahead of print].

Apicomplexans are a diverse phylum of unicellular eukaryotes that share obligate relationships with terrestrial and aquatic animal hosts. Many well-studied apicomplexans are responsible for several deadly zoonotic and human diseases, most notably malaria caused by Plasmodium. Interest in the evolutionary origin of apicomplexans has also spurred recent work on other more deeply-branching lineages, especially gregarines and sister groups like squirmids and chrompodellids. But a full picture of apicomplexan evolution is still lacking several lineages, and one major, diverse lineage that is notably absent is the adeleorinids. Adeleorina apicomplexans comprises hundreds of described species that infect invertebrate and vertebrate hosts across the globe. Although historically considered coccidians, phylogenetic trees based on limited data have shown conflicting branch positions for this subgroup, leaving this question unresolved. Phylogenomic trees and large-scale analyses comparing cellular functions and metabolism between major subgroups of apicomplexans have not incorporated Adeleorina because only a handful of molecular markers and a couple organellar genomes are available, ultimately excluding this group from contributing to our understanding of apicomplexan evolution and biology. To address this gap, we have generated complete genomes from mitochondria and plastids, as well as multiple deep-coverage single-cell transcriptomes of nuclear genes from two Adeleorina species, Klossia helicina and Legerella nova, and inferred a 206-protein phylogenomic tree of Apicomplexa. We observed distinct structures reported in species descriptions as remnant host structures surrounding adeleorinid oocysts. Klossia helicina and L. nova branched, as expected, with monoxenous adeleorinids within the Adeleorina and their mitochondrial and plastid genomes exhibited similarity to published organellar adeleorinid genomes. We show with a phylogeneomic tree and subsequent phylogenomic analyses that Adeleorina are not closely related to any of the currently sampled apicomplexan subgroups, and instead fall as a sister to a large clade encompassing Coccidia, Protococcidia, Hematozoa, and Nephromycida, collectively. This resolves Adeleorina as a key independently-branching group, separate from coccidians, on the tree of Apicomplexa, which now has all known major lineages sampled.

RevDate: 2024-03-15
CmpDate: 2024-03-15

Ghamizi M, Falniowski A, Boudellah A, et al (2024)

Two new genera and species of the valvatiform hydrobiid snails (Caenogastropoda: Truncatelloidea: Hydrobiidae) from Morocco.

Zootaxa, 5418(3):223-239.

Stygobiont and crenobiont minute gastropods representing the family Hydrobiidae (Caenogastropoda: Truncatelloidea), characterized by the valvatoid low-spired shell, were collected from one spring and four wells in Bouregreg region, NW Morocco. The shells were photographed and measured; shell biometry is illustrated with principal component analysis. Penes were illustrated and described. Mitochondrial cytochrome oxidase subunit 1 (COI) and 16S rRNA, as well as nuclear 18S rRNA sequences were used to infer the phylogeny. The snails represented two genera, both new to science. Their closest relatives were taxa from the Iberian Peninsula, the rough molecular estimate of the time of divergence between these Moroccan and Iberian genera coincided with the Pliocene Flooding, which restored the Strait of Gibraltar to connect the Mediterranean Basin with Atlantic Ocean.

RevDate: 2024-03-15
CmpDate: 2024-03-15

Gordon DP, Quek ZBR, D Huang (2024)

Four new species and a ribosomal phylogeny of Rhabdopleura (Hemichordata: Graptolithina) from New Zealand, with a review and key to all described extant taxa.

Zootaxa, 5424(3):323-357.

All eight extant species ofRhabdopleuradescribed between 1869 and 2018 are provisionally accepted as valid based on a review of the literature and new data on two little-known species from the Azores. Additionally, four new species are described from the New Zealand region, increasing global diversity by 50%, and a dichotomous key to all 12 described species is provided based on morphological criteria. The distinction between colony morphologies based on erect-tube inception is regarded as particularly helpful in initial characterization of species. Erect ringed tubes are either produced directly from the surface of creeping-tubes or indirectly, i.e. a short adherent side branch from a creeping tube is interpolated between the creeping tube and an erect tube; such side branches are blind-ending. These two modes of erect-tube origination are here respectively termeddirectandindirect. Species with indirect erect-tube budding are predominant in the North Atlantic whereas species with direct erect-tube budding dominate in New Zealand waters. The only indirect-erect species from New Zealand, Rhabdopleura chathamica n. sp., was discovered on deepwater coral from 10081075 m, constituting the deepest record of the genus to date. Rhabdopleura emancipata n. sp., collected only in a detached state, constitutes a three-dimensional tangled growth that grew freely into the water columna unique morphology hitherto unknown among extant species. Owing to this growth mode, it provided a substratum for epibionts from several phyla. Rhabdopleura francesca n. sp. and Rhabdopleura decipula n. sp. are morphologically very similar but are distinguishable by their distinct placements in a phylogeny based on 16S mitochondrial and 18S nuclear rRNA genes. Phylogenetic reconstructions based on rRNA and mitochondrial genome data contribute to an updated phylogeny of all Rhabdopleura species sequenced thus far, some of which require more molecular sequences and morphological analyses for taxonomic determination.

RevDate: 2024-03-15
CmpDate: 2024-03-15

Methou P, Chen C, T Komai (2024)

Revision of the alvinocaridid shrimp genus Rimicaris Williams & Rona, 1986 (Decapoda: Caridea) with description of a new species from the Mariana Arc hydrothermal vents.

Zootaxa, 5406(4):501-518.

A new species of alvinocaridid shrimp is reported, from the Northwest Eifuku hydrothermal vent field at 16191667 m depth on the Mariana Arc. A comprehensive phylogenetic reconstruction of Alvinocarididae based on the mitochondrial cytochrome c oxidase subunit I (COI) gene including this new species reveals the paraphyly of the genus Rimicaris Williams & Rona, 1986 with four other generaAlvinocaridinides, Manuscaris, Opaepele, and Shinkaicarisnested within it. We re-examine material of these four problematic genera, and synonymise them under Rimicaris whose diagnosis has been amended, in order to maintain a monophyletic Rimicaris. Our new species, Rimicaris cambonae sp. nov. is genetically close to Rimicaris loihi (Williams & Dobbs, 1995) comb. nov. (previously Opaepele loihi) with which it co-occurs, but can be morphologically distinguished by the less elevated dorsal surface of the rostrum, this being devoid of a median carina, a stronger pterygostomial tooth on the carapace, and a blunt rather than acuminate proximolateral process on the antennular stylocerite. Species previously assigned to the above listed, synonymized genera are also discussed, with new material examined for three key species: R. loihi, R. acuminata, and R. leurokolos. Further, Alvinocaridinides formosa Komai & Chan, 2010 and Manuscaris liui Wang & Sha, 2016 are synonymized under Rimicaris leurokolos (Kikuchi & Hashimoto, 2000) comb. nov. and R. acuminata (Komai & Tsuchida, 2015) comb. nov., respectively. Revised diagnoses are presented for R. loihi, R. acuminata, and R. leurokolos. After the present revision revision, Rimicaris now consists of 15 species.

RevDate: 2024-03-14
CmpDate: 2024-03-14

Vesala L, Basikhina Y, Tuomela T, et al (2024)

Mitochondrial perturbation in immune cells enhances cell-mediated innate immunity in Drosophila.

BMC biology, 22(1):60.

BACKGROUND: Mitochondria participate in various cellular processes including energy metabolism, apoptosis, autophagy, production of reactive oxygen species, stress responses, inflammation and immunity. However, the role of mitochondrial metabolism in immune cells and tissues shaping the innate immune responses are not yet fully understood. We investigated the effects of tissue-specific mitochondrial perturbation on the immune responses at the organismal level. Genes for oxidative phosphorylation (OXPHOS) complexes cI-cV were knocked down in the fruit fly Drosophila melanogaster, targeting the two main immune tissues, the fat body and the immune cells (hemocytes).

RESULTS: While OXPHOS perturbation in the fat body was detrimental, hemocyte-specific perturbation led to an enhanced immunocompetence. This was accompanied by the formation of melanized hemocyte aggregates (melanotic nodules), a sign of activation of cell-mediated innate immunity. Furthermore, the hemocyte-specific OXPHOS perturbation induced immune activation of hemocytes, resulting in an infection-like hemocyte profile and an enhanced immune response against parasitoid wasp infection. In addition, OXPHOS perturbation in hemocytes resulted in mitochondrial membrane depolarization and upregulation of genes associated with the mitochondrial unfolded protein response.

CONCLUSIONS: Overall, we show that while the effects of mitochondrial perturbation on immune responses are highly tissue-specific, mild mitochondrial dysfunction can be beneficial in immune-challenged individuals and contributes to variation in infection outcomes among individuals.

RevDate: 2024-03-14
CmpDate: 2024-03-14

Lanza A, Kimura S, Hirono I, et al (2024)

Transcriptome analysis of Edwardsiella piscicida during intracellular infection reveals excludons are involved with the activation of a mitochondrion-like energy generation program.

mBio, 15(3):e0352623.

Phylogenetic evidence suggests a shared ancestry between mitochondria and modern Proteobacteria, a phylum including several genera of intracellular pathogens. Studying these diverse pathogens, particularly during intracellular infection of their hosts, can reveal characteristics potentially representative of the mitochondrial-Proteobacterial ancestor by identifying traits shared with mitochondria. While transcriptomic approaches can provide global insights into intracellular acclimatization by pathogens, they are often limited by excess host RNAs in extracts. Here, we developed a method employing magnetic nanoparticles to enrich RNA from an intracellular Gammaproteobacterium, Edwardsiella piscicida, within zebrafish, Danio rerio, fin fibroblasts, enabling comprehensive exploration of the bacterial transcriptome. Our findings revealed that the intracellular E. piscicida transcriptome reflects a mitochondrion-like energy generation program characterized by the suppression of glycolysis and sugar transport, coupled with upregulation of the tricarboxylic acid (TCA) cycle and alternative import of simple organic acids that directly flux into TCA cycle intermediates or electron transport chain donors. Additionally, genes predicted to be members of excludons, loci of gene pairs antagonistically co-regulated by overlapping antisense transcription, are significantly enriched in the set of all genes with perturbed sense and antisense transcription, suggesting a general but important involvement of excludons with intracellular acclimatization. Notably, genes involved with the activation of the mitochondrion-like energy generation program, specifically with metabolite import and glycolysis, are also members of predicted excludons. Other intracellular Proteobacterial pathogens appear to employ a similar mitochondrion-like energy generation program, suggesting a potentially conserved mechanism for optimized energy acquisition from hosts centered around the TCA cycle.IMPORTANCEPhylogenetic evidence suggests that mitochondria and Proteobacteria, a phylum encompassing various intracellular pathogens, share a common ancestral lineage. In this study, we developed a novel method employing magnetic nanoparticles to explore the transcriptome of an aquatic Gammaproteobacterium, Edwardsiella piscicida, during intracellular infection of host cells. We show that the strategy E. piscicida uses to generate energy strikingly mirrors the function of mitochondria-energy generators devoid of glycolytic processes. Notably, several implicated genes are members of excludons-gene pairs antagonistically co-regulated by overlapping antisense transcription. Other intracellular Proteobacterial pathogens appear to adopt a similar mitochondrion-like energy generation program, indicating a possibly conserved strategy for optimized energy acquisition from hosts centered around the tricarboxylic acid cycle.

RevDate: 2024-03-13

Mourokh L, J Friedman (2024)

Mitochondria at the Nanoscale: Physics Meets Biology-What Does It Mean for Medicine?.

International journal of molecular sciences, 25(5): pii:ijms25052835.

Mitochondria are commonly perceived as "cellular power plants". Intriguingly, power conversion is not their only function. In the first part of this paper, we review the role of mitochondria in the evolution of eukaryotic organisms and in the regulation of the human body, specifically focusing on cancer and autism in relation to mitochondrial dysfunction. In the second part, we overview our previous works, revealing the physical principles of operation for proton-pumping complexes in the inner mitochondrial membrane. Our proposed simple models reveal the physical mechanisms of energy exchange. They can be further expanded to answer open questions about mitochondrial functions and the medical treatment of diseases associated with mitochondrial disorders.

RevDate: 2024-03-13
CmpDate: 2024-03-13

Bľandová G, Janoštiaková N, Kodada D, et al (2024)

Mitochondrial DNA variability and Covid-19 in the Slovak population.

Mitochondrion, 75:101827.

Recent studies have shown that mitochondria are involved in the pathogenesis of Covid-19. Mitochondria play a role in production of reactive oxygen species and induction of an innate immune response, both important during infections. Common variability of mitochondrial DNA (mtDNA) can affect oxidative phosphorylation and the risk or lethality of cardiovascular, neurodegenerative diseases and sepsis. However, it is unclear whether susceptibility of severe Covid-19 might be affected by mtDNA variation. Thus, we have analyzed mtDNA in a sample of 446 Slovak patients hospitalized due to Covid-19 and a control population group consisting of 1874 individuals. MtDNA variants in the HVRI region have been analyzed and classified into haplogroups at various phylogenetic levels. Binary logistic regression was used to assess the risk of Covid-19. Haplogroups T1, H11, K and variants 16256C > T, 16265A > C, 16293A > G, 16311 T > C and 16399A > G were associated with an increased Covid-19 risk. On contrary, Haplogroup J1, haplogroup clusters H + U5b and T2b + U5b, and the mtDNA variant 16189 T > C were associated with decreased risk of Covid-19. Following the application of the Bonferroni correction, statistical significance was observed exclusively for the cluster of haplogroups H + U5b. Unsurprisingly, the most significant factor contributing to the mortality of patients with Covid-19 is the age of patients. Our findings suggest that mtDNA haplogroups can play a role in Covid-19 pathogenesis, thus potentially useful in identifying susceptibility to its severe form. To confirm these associations, further studies taking into account the nuclear genome or other non-biological influences are needed.

RevDate: 2024-03-13

Fernández MB, Bleidorn C, LA Calcaterra (2022)

Wolbachia Infection in Native Populations of the Invasive Tawny Crazy Ant Nylanderia fulva.

Frontiers in insect science, 2:905803.

Antagonistic interactions can affect population growth and dispersal of an invasive species. Wolbachia are intracellular endosymbiont bacteria that infect arthropod and nematode hosts and are able to manipulate reproduction, which in some cases leads to cocladogenesis. Moreover, the presence of the strictly maternally transferred Wolbachia in a population can indirectly induce selective sweeps on the hosts' mitochondria. Ants have a Wolbachia infection rate of about 34%, which makes phylogenetic studies using mitochondrial markers vulnerable of being confounded by the effect of the endosymbiont. Nylanderia fulva is an invasive ant native to South America, considered a pest in the United States. Its distribution and biology are poorly known in its native range, and the taxonomic identity of this and its closely related species, Nylanderia pubens, has only recently been understood with the aid of molecular phylogenies. Aiming at estimating robust phylogenetic relationships of N. fulva in its native range, we investigated the presence and pattern of Wolbachia infection in populations of N. fulva from Argentina, part of its native range, to account for its possible effect on the host population structure. Using the ftsZ gene, 30 nests of N. fulva and four from sympatric Nylanderia species were screened for the presence of Wolbachia. We sequenced the MLST genes, the highly variable gene wsp, as well as glyQ, a novel target gene for which new primers were designed. Phylogeny of the ants was estimated using mtDNA (COI). We found supergroup A Wolbachia strains infecting 73% of N. fulva nests and two nests of Nylanderia sp. 1. Wolbachia phylogenetic tree inferred with MLST genes is partially congruent with the host phylogeny topology, with the exception of a lineage of strains shared by ants from different N. fulva clades. Furthermore, by comparing with Wolbachia sequences infecting other ants, we found that the strains infecting different N. fulva clades are not monophyletic. Our findings suggest there are three recent independent horizontally transmitted Wolbachia infections in N. fulva, and we found no evidence of influence of Wolbachia in the host mtDNA based phylogeny.

RevDate: 2024-03-12

Iverson ENK (2024)

Conservation Mitonuclear Replacement: Facilitated mitochondrial adaptation for a changing world.

Evolutionary applications, 17(3):e13642.

Most species will not be able to migrate fast enough to cope with climate change, nor evolve quickly enough with current levels of genetic variation. Exacerbating the problem are anthropogenic influences on adaptive potential, including the prevention of gene flow through habitat fragmentation and the erosion of genetic diversity in small, bottlenecked populations. Facilitated adaptation, or assisted evolution, offers a way to augment adaptive genetic variation via artificial selection, induced hybridization, or genetic engineering. One key source of genetic variation, particularly for climatic adaptation, are the core metabolic genes encoded by the mitochondrial genome. These genes influence environmental tolerance to heat, drought, and hypoxia, but must interact intimately and co-evolve with a suite of important nuclear genes. These coadapted mitonuclear genes form some of the important reproductive barriers between species. Mitochondrial genomes can and do introgress between species in an adaptive manner, and they may co-introgress with nuclear genes important for maintaining mitonuclear compatibility. Managers should consider the relevance of mitonuclear genetic variability in conservation decision-making, including as a tool for facilitating adaptation. I propose a novel technique dubbed Conservation Mitonuclear Replacement (CmNR), which entails replacing the core metabolic machinery of a threatened species-the mitochondrial genome and key nuclear loci-with those from a closely related species or a divergent population, which may be better-adapted to climatic changes or carry a lower genetic load. The most feasible route to CmNR is to combine CRISPR-based nuclear genetic editing with mitochondrial replacement and assisted reproductive technologies. This method preserves much of an organism's phenotype and could allow populations to persist in the wild when no other suitable conservation options exist. The technique could be particularly important on mountaintops, where rising temperatures threaten an alarming number of species with almost certain extinction in the next century.

RevDate: 2024-03-12
CmpDate: 2024-03-11

Ovciarikova J, Shikha S, Lacombe A, et al (2024)

Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites.

The Journal of cell biology, 223(4):.

Coordination between nucleus and mitochondria is essential for cell survival, and thus numerous communication routes have been established between these two organelles over eukaryotic cell evolution. One route for organelle communication is via membrane contact sites, functional appositions formed by molecular tethers. We describe a novel nuclear-mitochondrial membrane contact site in the protozoan Toxoplasma gondii. We have identified specific contacts occurring at the nuclear pore and demonstrated an interaction between components of the nuclear pore and the mitochondrial protein translocon, highlighting them as molecular tethers. Genetic disruption of the nuclear pore or the TOM translocon components, TgNup503 or TgTom40, respectively, result in contact site reduction, supporting their potential involvement in this tether. TgNup503 depletion further leads to specific mitochondrial morphology and functional defects, supporting a role for nuclear-mitochondrial contacts in mediating their communication. The discovery of a contact formed through interaction between two ancient mitochondrial and nuclear complexes sets the ground for better understanding of mitochondrial-nuclear crosstalk in eukaryotes.

RevDate: 2024-03-08

Kutzer MAM, Cornish B, Jamieson M, et al (2024)

Mitochondrial background can explain variable costs of immune deployment.

Journal of evolutionary biology pii:7624384 [Epub ahead of print].

Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology), or to a sterile control, and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation between lifespan and the proportion of time cybrids spent moving while alive. Our results suggests that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.

RevDate: 2024-03-07

Speijer D (2024)

How mitochondrial cristae illuminate the important role of oxygen during eukaryogenesis.

BioEssays : news and reviews in molecular, cellular and developmental biology [Epub ahead of print].

Inner membranes of mitochondria are extensively folded, forming cristae. The observed overall correlation between efficient eukaryotic ATP generation and the area of internal mitochondrial inner membranes both in unicellular organisms and metazoan tissues seems to explain why they evolved. However, the crucial use of molecular oxygen (O2) as final acceptor of the electron transport chain is still not sufficiently appreciated. O2 was an essential prerequisite for cristae development during early eukaryogenesis and could be the factor allowing cristae retention upon loss of mitochondrial ATP generation. Here I analyze illuminating bacterial and unicellular eukaryotic examples. I also discuss formative influences of intracellular O2 consumption on the evolution of the last eukaryotic common ancestor (LECA). These considerations bring about an explanation for the many genes coming from other organisms than the archaeon and bacterium merging at the start of eukaryogenesis.

RevDate: 2024-03-04
CmpDate: 2024-03-04

Yu TS, Park K, Han KH, et al (2024)

Morphological and genetic analysis for the diversity conservation of rare species, Thamnaconus multilineatus (Tetraodontiformes: Monacanthidae).

PloS one, 19(2):e0292916.

Climate changes have altered biodiversity and ultimately induced community changes that have threatened the survival of certain aquatic organisms such as fish species. Obtaining biological and genetic information on endangered fish species is critical for ecological population management. Thamnaconus multilineatus, registered as an endangered species by the IUCN in 2019, is a Data Deficient (DD) species with a remarkably small number of habitats worldwide and no known information other than its habitat and external form. In this study, we characterized the external and osteological morphology of a T. multilineatus specimen collected from eastern Jeju Island, South Korea, in 2020. We also investigated the phylogenetic relationships among related fish species through complete mitochondrial DNA (mtDNA) analysis of the T. multilineatus specimen. The external and skeletal characteristics of T. multilineatus were similar to those of previous reports describing other fish of the genus Thamnaconus, making it difficult to classify T. multilineatus as a similar species based only on morphological characteristics. As a result of analyzing the complete mtDNA of T. multilineatus, the length of the mtDNA was determined to be 16,435 bp, and the mitochondrial genome was found to have 37 CDCs, including 13 PCGs, 22 tRNAs, and 2 rRNAs. In the phylogenetic analysis within the suborder Balistoidei, T. multilineatus mtDNA formed a cluster with fish of the genus Thamnaconus. This study is the first to report on the skeletal structure and complete mtDNA of T. multilineatus. Since the current research on T. multilineatus has only been reported on morphology, the results of this study will be utilized as important information for the management and restoration of T. multilineatus as an endangered species and significant fishery resource.

RevDate: 2024-03-07

Alcantara da Silva JV, Ispada J, Nociti RP, et al (2024)

The central role of pyruvate metabolism on the epigenetic maturation and transcriptional profile of bovine oocytes.

Reproduction (Cambridge, England), 167(4): pii:REP-23-0181.

IN BRIEF: Pyruvate metabolism is one of the main metabolic pathways during oocyte maturation. This study demonstrates that pyruvate metabolism also regulates the epigenetic and molecular maturation in bovine oocytes.

ABSTRACT: Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus-oocyte complexes were cultured in vitro for 24 h, considering three experimental groups: Control (IVM medium only), DCA (IVM supplemented with sodium dichloroacetate, a stimulant of pyruvate oxidation into acetyl-CoA), or IA (IVM supplemented with sodium iodoacetate, a glycolysis inhibitor). The results revealed significant alterations in oocyte metabolism in both treatments, promoting the utilization of lipids as an energy source. These changes during IVM affected the dynamics of H3K9ac, subsequently influencing the oocyte's transcriptional activity. In the DCA and IA groups, a total of 148 and 356 differentially expressed genes were identified, respectively, compared to the control group. These findings suggest that modifications in pyruvate metabolism trigger the activation of metabolic pathways, particularly lipid metabolism, changing acetyl-CoA availability and H3K9ac levels, ultimately impacting the mRNA content of in vitro matured bovine oocytes.

RevDate: 2024-02-29

Chen Z, Xie X, Jia C, et al (2024)

Concentration-Driven Evolution of Adaptive Artificial Ion Channels or Nanopores with Specific Anticancer Activities.

Angewandte Chemie (International ed. in English) [Epub ahead of print].

In nature, ceramides are a class of sphingolipids possessing a unique ability to self-assemble into protein-permeable channels with intriguing concentration-dependent adaptive channel cavities. However, within the realm of artificial ion channels, this interesting phenomenon is scarcely recaptured. Herein, we report on a novel class of adaptive artificial channels, Pn-TPPs, based on PEGylated cholic acids bearing triphenylphosphonium (TPP) groups as anion binding motifs. Interestingly, the molecules self-assemble into chloride ion channels at low concentrations, while transforming into small molecule-permeable nanopores at high concentrations. Moreover, the TPP groups endow the molecules with mitochondria-targeting property, enabling them to selectively drill holes on the mitochondrial membrane of cancer cells and subsequently trigger the caspase 9 apoptotic pathway. The anticancer efficacies of Pn-TPPs correlate with their abilities to form nanopores. Significantly, the most active ensembles formed by P5-TPP exhibits impressive anticancer activity against human liver cancer cells, with an IC50 value of 3.8 μM. While demonstrating similar anticancer performance to doxorubicin, P5-TPP exhibits a selectivity index surpassing that of doxorubicin by a factor of 16.8.

RevDate: 2024-02-27

Xu L, Wang J, Zhang T, et al (2024)

Characterizing complete mitochondrial genome of Aquilegia amurensis and its evolutionary implications.

BMC plant biology, 24(1):142.

BACKGROUND: Aquilegia is a model system for studying the evolution of adaptive radiation. However, very few studies have been conducted on the Aquilegia mitochondrial genome. Since mitochondria play a key role in plant adaptation to abiotic stress, analyzing the mitochondrial genome may provide a new perspective for understanding adaptive evolution.

RESULTS: The Aquilegia amurensis mitochondrial genome was characterized by a circular chromosome and two linear chromosomes, with a total length of 538,736 bp; the genes included 33 protein-coding genes, 24 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. We subsequently conducted a phylogenetic analysis based on single nucleotide polymorphisms (SNPs) in the mitochondrial genomes of 18 Aquilegia species, which were roughly divided into two clades: the European-Asian clade and the North American clade. Moreover, the genes mttB and rpl5 were shown to be positively selected in European-Asian species, and they may help European and Asian species adapt to environmental changes.

CONCLUSIONS: In this study, we assembled and annotated the first mitochondrial genome of the adaptive evolution model plant Aquilegia. The subsequent analysis provided us with a basis for further molecular studies on Aquilegia mitochondrial genomes and valuable information on adaptive evolution in Aquilegia.

RevDate: 2024-02-27

Cardoso DC, Baldez BCL, Pereira AH, et al (2024)

De novo assembly of the complete mitochondrial genome of Mycetophylax simplex Emery, 1888 through organelle targeting revels no substantial expansion of gene spacers, but rather some slightly shorter genes.

Molecular genetics and genomics : MGG, 299(1):16.

Mitochondria play a key role in cell biology and have their own genome, residing in a highly oxidative environment that induces faster changes than the nuclear genome. Because of this, mitochondrial markers have been exploited to reconstruct phylogenetic and phylogeographic relationships in studies of adaptation and molecular evolution. In this study, we determined the complete mitogenome of the fungus-farming ant Mycetophylax simplex (Hymenoptera, Formicidae) and conducted a comparative analysis among 29 myrmicine ant mitogenomes. Mycetophylax simplex is an endemic ant that inhabits sand dunes along the southern Atlantic coast. Specifically, the species occur in the ecosystem known as "restinga", within the Atlantic Forest biome. Due to habitat degradation, land use and decline of restinga habitats, the species is considered locally extinct in extremely urban beaches and is listed as vulnerable on the Brazilian Red List (ICMBio). We employed a mitochondrion-targeting approach to obtain the complete mitogenome through high-throughput DNA sequencing technology. This method allowed us to determine the mitogenome with high performance, coverage and low cost. The circular mitogenome has a length of 16,367 base pairs enclosing 37 genes (13 protein-coding genes, 22 tRNAs and 2 rRNAs) along with one control region (CR). All the protein-coding genes begin with a typical ATN codon and end with the canonical stop codons. All tRNAs formed the fully paired acceptor stems and fold into the typical cloverleaf-shaped secondary structures. The gene order is consistent with the shared Myrmicinae structure, and the A + T content of the majority strand is 81.51%. Long intergenic spacers were not found but some gene are slightly shorter. The phylogenetic relationships based on concatenated nucleotide and amino acid sequences of the 13 protein-coding genes, using Maximum Likelihood and Bayesian Inference methods, indicated that mitogenome sequences were useful in resolving higher-level relationship within Formicidae.

RevDate: 2024-02-27

Selosse MA (2024)

[Mitochondria, organelles or bacteria?].

Medecine sciences : M/S, 40(2):197-198.

RevDate: 2024-02-27

Micchelli CE, Percopo C, Traver M, et al (2024)

Progressive heterogeneity of enlarged and irregularly shaped apicoplasts in P. falciparum persister blood stages after drug treatment.

bioRxiv : the preprint server for biology pii:2024.01.03.574077.

UNLABELLED: Morphological modifications and shifts in organelle relationships are hallmarks of dormancy in eukaryotic cells. Communications between altered mitochondria and nuclei are associated with metabolic quiescence of cancer cells that can survive chemotherapy. In plants, changes in the pathways between nuclei, mitochondria, and chloroplasts are associated with cold stress and bud dormancy. Plasmodium falciparum parasites, the deadliest agent of malaria in humans, contain a chloroplast-like organelle (apicoplast) derived from an ancient photosynthetic symbiont. Antimalarial treatments can fail because a small fraction of the blood stage parasites enter dormancy and recrudesce after drug exposure. Altered mitochondrial-nuclear interactions in these persisters have been described for P. falciparum , but interactions of the apicoplast remained to be characterized. In the present study, we examined the apicoplasts of dormant persisters obtained after exposure to dihydroartemisinin (a first-line antimalarial drug) followed by sorbitol treatment, or after exposure to sorbitol treatment alone. As previously observed, the mitochondrion of persisters was consistently enlarged and in close association with the nucleus. In contrast, the apicoplast varied from compact and oblate, like those of active ring stage parasites, to enlarged and irregularly shaped. Enlarged apicoplasts became more prevalent later in dormancy, but regular size apicoplasts subsequently predominated when actively replicating parasites recrudesced. All three organelles, nucleus, mitochondrion, and apicoplast, became closer during dormancy. Understanding their relationships in erythrocytic-stage persisters may lead to new strategies to prevent recrudescences and protect the future of malaria chemotherapy.

SIGNIFICANCE STATEMENT: Dormancy of blood-stage malaria parasites (as persister forms) frequently undermines treatment and may facilitate the evolution of drug resistance. Here, we examine changes that occur in dormancy with two P. falciparum organelles relative to the nucleus: the mitochondrion and the plastid-like apicoplast. As previously reported, the mitochondrion of persisters is consistently enlarged, irregularly shaped, and shifted into close apposition with the nucleus. However, apicoplasts exhibit a greater variety of shapes, volumes, and relative positioning during dormancy: some persisters maintain a regular appearing apicoplast, while others show dramatically altered apicoplasts, reminiscent of the chloroplast swelling and degradation that occurs with death from reactive oxygen species in various plant cells. Improved understanding of these processes will support new approaches in antimalarial chemotherapy.

RevDate: 2024-02-26
CmpDate: 2024-02-26

Li G, Zhang H, Lin Z, et al (2024)

Comparative analysis of chloroplast and mitochondrial genomes of sweet potato provides evidence of gene transfer.

Scientific reports, 14(1):4547.

The increasing number of plant mitochondrial DNA genomes (mtDNA) sequenced reveals the extent of transfer from both chloroplast DNA genomes (cpDNA) and nuclear DNA genomes (nDNA). This study created a library and assembled the chloroplast and mitochondrial genomes of the leafy sweet potato better to understand the extent of mitochondrial and chloroplast gene transfer. The full-length chloroplast genome of the leafy sweet potato (OM808940) is 161,387 bp, with 132 genes annotated, including 87 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The mitochondrial genome (OM808941) was 269,578 bp in length and contained 69 functional genes, including 39 protein-coding genes, 6 rRNA genes, and 24 tRNA genes. 68 SSR loci were found in the leafy sweet potato organelle genome, including 54 in the chloroplast genome and 14 in the mitochondria genome. In the sweet potato mitochondrial genome, most genes have RNA editing sites, and the conversion ratio from hydrophilic amino acids to hydrophobic amino acids is the highest, reaching 47.12%. Horizontal transfer occurs in the sweet potato organelle genome and nuclear genome. 40 mitochondrial genome segments share high homology with 14 chloroplast genome segments, 33 of which may be derived from chloroplast genome horizontal transfer. 171 mitochondrial genome sequences come from the horizontal transfer of nuclear genome. The phylogenetic analysis of organelle genes revealed that the leafy sweet potato was closely related to the tetraploid wild species Ipomoea tabascana and the wild diploid species Ipomoea trifida.

RevDate: 2024-02-25

Xu R, Li T, Luo J, et al (2024)

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells.

CNS neuroscience & therapeutics, 30(2):e14640.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a novel lipid-lowing target. Recent clinical studies suggested the value of inhibiting PCSK9 in decreasing the vulnerability of coronary plaques. However, the evidence of PCSK9-regulated evolution of unstable carotid plaques is unclear, which has limited the use of PCSK9 inhibitor in carotid plaques. This study aimed to determine the effect and molecular mechanisms of PCSK9 on vulnerability of carotid plaques, to provide potential therapeutic targets for stabilizing carotid plaques.

METHODS: The expression of PCSK9 in stable and unstable carotid plaques were examined in tissue and plasma. Human aortic vascular smooth muscle cells (VSMCs) and carotid VSMCs were employed to transfect lentivirus for overexpression and knockdown of PCSK9, respectively. Morphological and functional changes of mitochondria were observed by live-cell imaging. Cell apoptosis was evaluated by propidium iodide staining. RNA-sequencing and biological examinations were performed to explore and validate the underlying mechanisms. Truncated plasmids were employed to identify the functional domain of PCSK9 in regulation of VSMCs' mitochondrial morphology, function and apoptosis.

RESULTS: Clinically, PCSK9 was closely related with vulnerability of human carotid plaques. Increased expression of PCSK9 in human VSMCs was accompanied by higher level of apoptosis. At subcellular level of VSMCs, the morphology of mitochondria was shifted toward the fission state, followed by mitochondrial dysfunction. Inhibition of p38 MAPK activation partially rescued the above morphological and behavioral changes caused by PCSK9. Furthermore, inhibiting of dynamin-related protein 1 (DRP1) attenuated PCSK9-related mitochondrial dysfunction and cell apoptosis. The 1-149aa domain of PCSK9 protein was essential to achieve functional regulation to VSMCs.

CONCLUSION: Our findings demonstrated that PCSK9 induced morphology-related mitochondrial dysfunction and apoptosis of VSMCs, which may be related to increased vulnerability of carotid plaque.

RevDate: 2024-02-23

Kan S, Liao X, Lan L, et al (2024)

Cytonuclear interactions and subgenome dominance shape the evolution of organelle-targeted genes in the Brassica triangle of U.

Molecular biology and evolution pii:7613086 [Epub ahead of print].

The interaction and co-evolution between nuclear and cytoplasmic genomes are one of the fundamental hallmarks of eukaryotic genome evolution and, two billion years later, are still major contributors to the formation of new species. Although many studies have investigated the role of cytonuclear interactions following allopolyploidization, the relative magnitude of the effect of subgenome dominance vs. cytonuclear interaction on genome evolution remains unclear. The Brassica triangle of U features three diploid species that together have formed three separate allotetraploid species on similar evolutionary timescales, providing an ideal system for understanding the contribution of the cytoplasmic donor to hybrid polyploid. Here, we investigated the evolutionary pattern of organelle-targeted genes in B. carinata (BBCC) and two varieties of B. juncea (AABB) at the whole-genome level, with particular focus on cytonuclear enzyme complexes. We found partial evidence that plastid-targeted genes experience selection to match plastid genomes, but no obvious corresponding signal in mitochondria-targeted genes from these two separately formed allopolyploids. Interestingly, selection acting on plastid genomes always reduced the retention rate of plastid-targeted genes encoded by the B subgenome, regardless of whether the B. nigra (BB) subgenome was contributed by the paternal or maternal progenitor. More broadly, this study illustrates the distinct selective pressures experienced by plastid- and mitochondria-targeted genes, despite a shared pattern of inheritance and natural history. Our study also highlights an important role for subgenome dominance in allopolyploid genome evolution, even in genes whose function depends on separately inherited molecules.

RevDate: 2024-02-22
CmpDate: 2024-02-22

Li H, Akella S, Engstler C, et al (2024)

Recurrent evolutionary switches of mitochondrial cytochrome c maturation systems in Archaeplastida.

Nature communications, 15(1):1548.

Mitochondrial cytochrome c maturation (CCM) requires heme attachment via distinct pathways termed systems I and III. The mosaic distribution of these systems in Archaeplastida raises questions about the genetic mechanisms and evolutionary forces promoting repeated evolution. Here, we show a recurrent shift from ancestral system I to the eukaryotic-specific holocytochrome c synthase (HCCS) of system III in 11 archaeplastid lineages. Archaeplastid HCCS is sufficient to rescue mutants of yeast system III and Arabidopsis system I. Algal HCCS mutants exhibit impaired growth and respiration, and altered biochemical and metabolic profiles, likely resulting from deficient CCM and reduced cytochrome c-dependent respiratory activity. Our findings demonstrate that archaeplastid HCCS homologs function as system III components in the absence of system I. These results elucidate the evolutionary trajectory and functional divergence of CCM pathways in Archaeplastida, providing insight into the causes, mechanisms, and consequences of repeated cooption of an entire biological pathway.

RevDate: 2024-02-22
CmpDate: 2024-02-22

Khan MM, Suhail SM, Majid HA, et al (2024)

Morpometric and molecular characterization of Surguli goat through CO1 gene in district Kohat.

Animal biotechnology, 35(1):2290528.

The present study was designed with the aim to study morphometric characterization as well as phylogeny and diversity of the local Surguli goat at their breeding tract district Kohat through mitochondrial DNA region, i.e., Cytochrome C Oxidase Subunit One (CO1) gene. Morphometric data and blood samples were collected from thirty (30) pure goats. Morphometric analysis showed that sex had significant effect (p < 0.05) on body weight, body length, hearth girth and horn length while no significant effect (p > 0.05) was observed for other characteristics. The results also indicated that age had significant effect (p < 0.05) on height at rump, ear length, horn length and tail length while no significant effect (p > 0.05) was observed for other characteristics. The phylogenetic analysis through CO1 nucleotide sequences within nucleotide range 1-767 showed nine polymorphic sites segregating into eight haplotypes. The mean intraspecific diversity and mean interspecific diversity were calculated as 0.23 and 2.36%, respectively. Phylogenetic tree revealed that Capra Ibex and native Surguli goat have common ancestors. The morphometric and molecular results obtained from the present study can be exploited as a selection tool for breeding and overall improvement.

RevDate: 2024-02-17

Széliová D, Müller S, J Zanghellini (2024)

Costs of ribosomal RNA stabilization affect ribosome composition at maximum growth rate.

Communications biology, 7(1):196.

Ribosomes are key to cellular self-fabrication and limit growth rate. While most enzymes are proteins, ribosomes consist of 1/3 protein and 2/3 ribonucleic acid (RNA) (in E. coli).Here, we develop a mechanistic model of a self-fabricating cell, validated across diverse growth conditions. Through resource balance analysis (RBA), we explore the variation in maximum growth rate with ribosome composition, assuming constant kinetic parameters.Our model highlights the importance of RNA instability. If we neglect it, RNA synthesis is always cheaper than protein synthesis, leading to an RNA-only ribosome at maximum growth rate. Upon accounting for RNA turnover, we find that a mixed ribosome composed of RNA and proteins maximizes growth rate. To account for RNA turnover, we explore two scenarios regarding the activity of RNases. In (a) degradation is proportional to RNA content. In (b) ribosomal proteins cooperatively mitigate RNA instability by protecting it from misfolding and subsequent degradation. In both cases, higher protein content elevates protein synthesis costs and simultaneously lowers RNA turnover expenses, resulting in mixed RNA-protein ribosomes. Only scenario (b) aligns qualitatively with experimental data across varied growth conditions.Our research provides fresh insights into ribosome biogenesis and evolution, paving the way for understanding protein-rich ribosomes in archaea and mitochondria.

RevDate: 2024-02-16

Tetzlaff S, Hillebrand A, Drakoulis N, et al (2024)

Small RNAs from mitochondrial genome recombination sites are incorporated into T. gondii mitoribosomes.

eLife, 13: pii:95407 [Epub ahead of print].

The mitochondrial genomes of apicomplexans comprise merely three protein-coding genes, alongside a set of thirty to forty genes encoding small RNAs (sRNAs), many of which exhibit homologies to rRNA from E. coli. The expression status and integration of these short RNAs into ribosomes remains unclear and direct evidence for active ribosomes within apicomplexan mitochondria is still lacking. In this study, we conducted small RNA sequencing on the apicomplexan Toxoplasma gondii to investigate the occurrence and function of mitochondrial sRNAs. To enhance the analysis of sRNA sequencing outcomes, we also re-sequenced the T. gondii mitochondrial genome using an improved organelle enrichment protocol and Nanopore sequencing. It has been established previously that the T. gondii genome comprises 21 sequence blocks that undergo recombination among themselves but that their order is not entirely random. The enhanced coverage of the mitochondrial genome allowed us to characterize block combinations at increased resolution. Employing this refined genome for sRNA mapping, we find that many small RNAs originated from the junction sites between protein-coding blocks and rRNA sequence blocks. Surprisingly, such block border sRNAs were incorporated into polysomes together with canonical rRNA fragments and mRNAs. In conclusion, apicomplexan ribosomes are active within polysomes and are indeed assembled through the integration of sRNAs, including previously undetected sRNAs with merged mRNA-rRNA sequences. Our findings lead to the hypothesis that T. gondii's block-based genome organization enables the dual utilization of mitochondrial sequences as both messenger RNAs and ribosomal RNAs, potentially establishing a link between the regulation of rRNA and mRNA expression.

RevDate: 2024-02-16

Degli Esposti M (2024)

Did mitophagy follow the origin of mitochondria?.

Autophagy [Epub ahead of print].

Mitophagy is the process of selective autophagy that removes superfluous and dysfunctional mitochondria. Mitophagy was first characterized in mammalian cells and is now recognized to follow several pathways including basal forms in specific organs. Mitophagy pathways are regulated by multiple, often interconnected factors. The present review aims to streamline this complexity and evaluate common elements that may define the evolutionary origin of mitophagy. Key issues surrounding mitophagy signaling at the mitochondrial surface may fundamentally derive from mitochondrial membrane dynamics. Elements of such membrane dynamics likely originated during the endosymbiosis of the alphaproteobacterial ancestor of our mitochondria but underwent an evolutionary leap forward in basal metazoa that determined the currently known variations in mitophagy signaling.Abbreviations: AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase; ATG, autophagy related; BCL2L13, BCL2 like 13; BNIP3, BCL2 interacting protein 3; BNIP3L, BCL2 interacting protein 3 like; CALCOCO, calcium binding and coiled-coil domain; CL, cardiolipin; ER, endoplasmic reticulum; ERMES, ER-mitochondria encounter structure; FBXL4, F-box and leucine rich repeat protein 4; FUNDC1, FUN14 domain containing 1; GABARAPL1, GABA type A receptor associated protein like 1; HIF, hypoxia inducible factor; IMM, inner mitochondrial membrane; LBPA/BMP, lysobisphosphatidic acid; LIR, LC3-interacting region; LPA, lysophosphatidic acid; MAM, mitochondria-associated membranes; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MCL, monolysocardiolipin; ML, maximum likelihood; NBR1, NBR1 autophagy cargo receptor; OMM, outer mitochondrial membrane; PA, phosphatidic acid; PACS2, phosphofurin acidic cluster sorting protein 2; PC/PLC, phosphatidylcholine; PE, phosphatidylethanolamine; PHB2, prohibitin 2; PINK1, PTEN induced kinase 1; PtdIns, phosphatidylinositol; SAR, Stramenopiles, Apicomplexa and Rhizaria; TAX1BP1, Tax1 binding protein 1; ULK1, unc-51 like autophagy activating kinase 1; VDAC/porin, voltage dependent anion channel.

RevDate: 2024-02-14
CmpDate: 2024-02-14

Sharma A, Ahlawat S, Sharma R, et al (2023)

Tracing the genetic footprints: India's role as a gateway for pig migration and domestication across continents.

Animal biotechnology, 34(9):5173-5179.

This study explored the maternal genetic diversity in the pig genetic resources of India by analyzing a mitochondrial D-loop fragment and comparing it with the corresponding sequences of previously published studies involving domestic pigs and wild boars. Sequencing of 103 samples representing different domestic pig populations revealed existence of 32 maternal haplotypes. The indices of haplotype and nucleotide diversity in Indian domestic pigs were 0.9421 and 0.015, respectively. Median-Joining network revealed that Indian pigs belong to Clade A and show conformity to 6 haplogroups reported worldwide (D1a, D1a1, D1a2, D1e, D1h and D3a). Among these, D1e and D1a2 were shared with Asian wild boars too. Interestingly, haplotype sharing was evident between Indian pigs and samples from other countries representing Africa, Asia, Europe and Oceania. This study substantiates India's contribution as a possible pig domestication center and highlights the importance of the Indian subcontinent in dispersal of the species to other continents. Additionally, genetic evidence suggested the influence of trading routes and historical interactions in shaping pig genetic exchange. Overall, this investigation provides valuable insights into the genetic diversity, historical migration, and domestication of Indian domestic pigs, contributing to the broader understanding of global pig genetic resources and their evolutionary history.

RevDate: 2024-02-13

Choudhury C, Gill MK, McAleese CE, et al (2024)

The Arylamine N-Acetyltransferases as Therapeutic Targets in Metabolic Diseases Associated with Mitochondrial Dysfunction.

Pharmacological reviews, 76(2):300-320 pii:pharmrev.123.000835.

In humans, there are two arylamine N-acetyltransferase genes that encode functional enzymes (NAT1 and NAT2) as well as one pseudogene, all of which are located together on chromosome 8. Although they were first identified by their role in the acetylation of drugs and other xenobiotics, recent studies have shown strong associations for both enzymes in a variety of diseases, including cancer, cardiovascular disease, and diabetes. There is growing evidence that this association may be causal. Consistently, NAT1 and NAT2 are shown to be required for healthy mitochondria. This review discusses the current literature on the role of both NAT1 and NAT2 in mitochondrial bioenergetics. It will attempt to relate our understanding of the evolution of the two genes with biologic function and then present evidence that several major metabolic diseases are influenced by NAT1 and NAT2. Finally, it will discuss current and future approaches to inhibit or enhance NAT1 and NAT2 activity/expression using small-molecule drugs. SIGNIFICANCE STATEMENT: The arylamine N-acetyltransferases (NATs) NAT1 and NAT2 share common features in their associations with mitochondrial bioenergetics. This review discusses mitochondrial function as it relates to health and disease, and the importance of NAT in mitochondrial function and dysfunction. It also compares NAT1 and NAT2 to highlight their functional similarities and differences. Both NAT1 and NAT2 are potential drug targets for diseases where mitochondrial dysfunction is a hallmark of onset and progression.

RevDate: 2024-02-12

Fehsenfeld S, Yoon GR, Quijada-Rodriguez AR, et al (2024)

Short-term exposure to high pCO2 leads to decreased branchial cytochrome C oxidase activity in the presence of octopamine in a decapod.

Comparative biochemistry and physiology. Part A, Molecular & integrative physiology pii:S1095-6433(24)00030-8 [Epub ahead of print].

In a recent mechanistic study, octopamine was shown to promote proton transport over the branchial epithelium in green crabs, Carcinus maenas. Here, we follow up on this finding by investigating the involvement of octopamine in an environmental and physiological context that challenges acid-base homeostasis, the response to short-term high pCO2 exposure (400 Pa) in a brackish water environment. We show that hyperregulating green crabs experienced a respiratory acidosis as early as 6 h of exposure to hypercapnia, with a rise in hemolymph pCO2 accompanied by a simultaneous drop of hemolymph pH. The slightly delayed increase in hemolymph HCO3[-] observed after 24 h helped to restore hemolymph pH to initial values by 48 h. Circulating levels of the biogenic amine octopamine were significantly higher in short-term high pCO2 exposed crabs compared to control crabs after 48 h. Whole animal metabolic rates, intracellular levels of octopamine and cAMP, as well as branchial mitochondrial enzyme activities for complex I + III and citrate synthase were unchanged in posterior gill #7 after 48 h of hypercapnia. However, application of octopamine in gill respirometry experiments suppressed branchial metabolic rate in posterior gills of short-term high pCO2 exposed animals. Furthermore, branchial enzyme activity of cytochrome C oxidase decreased in high pCO2 exposed crabs after 48 h. Our results indicate that hyperregulating green crabs are capable of quickly counteracting a hypercapnia-induced respiratory acidosis. The role of octopamine in the acclimation of green crabs to short-term hypercapnia seems to entail the alteration of branchial metabolic pathways, possibly targeting mitochondrial cytochrome C in the gill. Our findings help advancing our current limited understanding of endocrine components in hypercapnia acclimation. SUMMARY STATEMENT: Acid-base compensation upon short-term high pCO2 exposure in hyperregulating green crabs started after 6 h and was accomplished by 48 h with the involvement of the biogenic amine octopamine, accumulation of hemolymph HCO3[-], and regulation of mitochondrial complex IV (cytochrome C oxidase).

RevDate: 2024-02-10

Guan J, Zhang Z, G Shi (2024)

Genome-Wide Identification of the Ferric Chelate Reductase (FRO) Gene Family in Peanut and Its Diploid Progenitors: Structure, Evolution, and Expression Profiles.

Plants (Basel, Switzerland), 13(3): pii:plants13030418.

The ferric chelate reductase (FRO) family plays a vital role in metal ion homeostasis in a variety of locations in the plants. However, little is known about this family in peanut (Arachis hypogaea). This study aimed to identify FRO genes from the genomes of peanut and the two diploid progenitors (A. duranensis and A. ipaensis) and to analyze their gene/protein structures and evolution. In addition, transcriptional responses of AhFRO genes to Fe deficiency and/or Cu exposure were investigated in two peanut cultivars with different Fe deficiency tolerance (Silihong and Fenghua 1). A total of nine, four, and three FRO genes were identified in peanut, A. duranensis, and A. ipaensis, respectively, which were divided into three groups. Most AhFRO genes underwent WGD/segmental duplication, leading to the expansion of the AhFRO gene family. In general, clustered members share similar gene/protein structures. However, significant divergences occurred in AhFRO2 genes. Three out of five AhFRO2 genes were lowly expressed in all tissues under normal conditions, which may be beneficial for avoiding gene loss. Transcription analysis revealed that AhFRO2 and AhFRO7 genes might be involved in the reduction of Fe/Cu in plasma membranes and plastids, respectively. AhFRO8 genes appear to confer Fe reduction in the mitochondria. Moreover, Fe deficiency induced an increase of Cu accumulation in peanut plants in which AhFRO2.2/2.4/2.5 and FRO7.1/7.2 might be involved. Our findings provided new clues for further understanding the roles of AhFRO genes in the Fe/Cu interaction in peanut.

RevDate: 2024-02-09

Wang Y, Li H, Niu G, et al (2024)

Boosting Sono-immunotherapy of Prostate Carcinoma through Amplifying Domino-Effect of Mitochondrial Oxidative Stress Using Biodegradable Cascade-Targeting Nanocomposites.

ACS nano [Epub ahead of print].

Sono-immunotherapy faces challenges from poor immunogenicity and low response rate due to complex biological barriers. Herein, we prepared MCTH nanocomposites (NCs) consisting of disulfide bonds (S-S) doped mesoporous organosilica (MONs), Cu-modified protoporphyrin (CuPpIX), mitochondria-targeting triphenylphosphine (TPP), and CD44-targeting hyaluronic acid (HA). MCTH NCs efficiently accumulate at the tumor site due to the overexpressed CD44 receptors on the membrane of the cancer cells. Under the function of HAase and glutathione (GSH), MCTH degrades and exposes TPP to deliver CuPpIX to the mitochondrial site and induce a reactive oxygen species (ROS) burst in situ under ultrasound irradiations, thereby causing severe mitochondria dysfunction. This cascade-targeting ability of MCTH NCs not only reinforces oxidative stress in cancer cells but also amplifies immunogenic cell death (ICD) to stimulate the body's immune response and alleviate the tumor immunosuppressive microenvironment. These NCs significantly enhance the infiltration of immune cells into the tumor, particularly CD8[+] T cells, for a powerful antitumor sono-immunotherapy. The proposed cascade-targeting strategy holds promise for strengthening sono-immunotherapy for prostate cancer treatment and overcoming the limitations of traditional immunotherapy.

RevDate: 2024-02-08

Iverson ENK, Criswell A, JC Havird (2024)

Stronger evidence for relaxed selection than adaptive evolution in high-elevation animal mtDNA.

bioRxiv : the preprint server for biology pii:2024.01.20.576402.

Mitochondrial (mt) genes are the subject of many adaptive hypotheses due to the key role of mitochondria in energy production and metabolism. One widespread adaptive hypothesis is that selection imposed by life at high elevation leads to the rapid fixation of beneficial alleles in mtDNA, reflected in the increased rates of mtDNA evolution documented in many high-elevation species. However, the assumption that fast mtDNA evolution is caused by positive, rather than relaxed purifying selection has rarely been tested. Here, we calculated the d N / d S ratio, a metric of nonsynonymous substitution bias, and explicitly tested for relaxed selection in the mtDNA of over 700 species of terrestrial vertebrates, freshwater fishes, and arthropods, with information on elevation and latitudinal range limits, range sizes, and body sizes. We confirmed that mitochondrial genomes of high-elevation taxa have slightly higher d N / d S ratios compared to low-elevation relatives. High-elevation species tend to have smaller ranges, which predict higher d N / d S ratios and more relaxed selection across species and clades, while absolute elevation and latitude do not predict higher d N / d S . We also find a positive relationship between body mass and d N / d S , supporting a role for small effective population size leading to relaxed selection. We conclude that higher mt d N / d S among high-elevation species is more likely to reflect relaxed selection due to smaller ranges and reduced effective population size than adaptation to the environment. Our results highlight the importance of rigorously testing adaptive stories against non-adaptive alternative hypotheses, especially in mt genomes.

RevDate: 2024-02-07

Murphy MP, LAJ O'Neill (2024)

A break in mitochondrial endosymbiosis as a basis for inflammatory diseases.

Nature, 626(7998):271-279.

Mitochondria retain bacterial traits due to their endosymbiotic origin, but host cells do not recognize them as foreign because the organelles are sequestered. However, the regulated release of mitochondrial factors into the cytosol can trigger cell death, innate immunity and inflammation. This selective breakdown in the 2-billion-year-old endosymbiotic relationship enables mitochondria to act as intracellular signalling hubs. Mitochondrial signals include proteins, nucleic acids, phospholipids, metabolites and reactive oxygen species, which have many modes of release from mitochondria, and of decoding in the cytosol and nucleus. Because these mitochondrial signals probably contribute to the homeostatic role of inflammation, dysregulation of these processes may lead to autoimmune and inflammatory diseases. A potential reason for the increased incidence of these diseases may be changes in mitochondrial function and signalling in response to such recent phenomena as obesity, dietary changes and other environmental factors. Focusing on the mixed heritage of mitochondria therefore leads to predictions for future insights, research paths and therapeutic opportunities. Thus, whereas mitochondria can be considered 'the enemy within' the cell, evolution has used this strained relationship in intriguing ways, with increasing evidence pointing to the recent failure of endosymbiosis being critical for the pathogenesis of inflammatory diseases.

RevDate: 2024-02-05
CmpDate: 2024-02-05

Gangavarapu K, Ji X, Baele G, et al (2024)

Many-core algorithms for high-dimensional gradients on phylogenetic trees.

Bioinformatics (Oxford, England), 40(2):.

MOTIVATION: Advancements in high-throughput genomic sequencing are delivering genomic pathogen data at an unprecedented rate, positioning statistical phylogenetics as a critical tool to monitor infectious diseases globally. This rapid growth spurs the need for efficient inference techniques, such as Hamiltonian Monte Carlo (HMC) in a Bayesian framework, to estimate parameters of these phylogenetic models where the dimensions of the parameters increase with the number of sequences N. HMC requires repeated calculation of the gradient of the data log-likelihood with respect to (wrt) all branch-length-specific (BLS) parameters that traditionally takes O(N2) operations using the standard pruning algorithm. A recent study proposes an approach to calculate this gradient in O(N), enabling researchers to take advantage of gradient-based samplers such as HMC. The CPU implementation of this approach makes the calculation of the gradient computationally tractable for nucleotide-based models but falls short in performance for larger state-space size models, such as Markov-modulated and codon models. Here, we describe novel massively parallel algorithms to calculate the gradient of the log-likelihood wrt all BLS parameters that take advantage of graphics processing units (GPUs) and result in many fold higher speedups over previous CPU implementations.

RESULTS: We benchmark these GPU algorithms on three computing systems using three evolutionary inference examples exploring complete genomes from 997 dengue viruses, 62 carnivore mitochondria and 49 yeasts, and observe a >128-fold speedup over the CPU implementation for codon-based models and >8-fold speedup for nucleotide-based models. As a practical demonstration, we also estimate the timing of the first introduction of West Nile virus into the continental Unites States under a codon model with a relaxed molecular clock from 104 full viral genomes, an inference task previously intractable.

We provide an implementation of our GPU algorithms in BEAGLE v4.0.0 (https://github.com/beagle-dev/beagle-lib), an open-source library for statistical phylogenetics that enables parallel calculations on multi-core CPUs and GPUs. We employ a BEAGLE-implementation using the Bayesian phylogenetics framework BEAST (https://github.com/beast-dev/beast-mcmc).

RevDate: 2024-02-02

Muñoz-Gómez SA (2024)

The energetic costs of cellular complexity in evolution.

Trends in microbiology pii:S0966-842X(24)00003-9 [Epub ahead of print].

The evolutionary history of cells has been marked by drastic increases in complexity. Some hypothesize that such cellular complexification requires a massive energy flux as the origin of new features is hypothetically more energetically costly than their evolutionary maintenance. However, it remains unclear how increases in cellular complexity demand more energy. I propose that the early evolution of new genes with weak functions imposes higher energetic costs by overexpression before their functions are evolutionarily refined. In the long term, the accumulation of new genes deviates resources away from growth and reproduction. Accrued cellular complexity further requires additional infrastructure for its maintenance. Altogether, this suggests that larger and more complex cells are defined by increased survival but lower reproductive capacity.

RevDate: 2024-02-02

McCallum Q, Askelson K, Fogarty FF, et al (2024)

Pronounced differentiation on the Z chromosome and parts of the autosomes in crowned sparrows contrasts with mitochondrial paraphyly: implications for speciation.

Journal of evolutionary biology pii:7512494 [Epub ahead of print].

When a single species evolves into multiple descendent species, some parts of the genome can play a key role in the evolution of reproductive isolation while other parts flow between the evolving species via interbreeding. Genomic evolution during the speciation process is particularly interesting when major components of the genome-for instance, sex chromosomes vs. autosomes vs. mitochondrial DNA-show widely differing patterns of relationships between three diverging populations. The golden-crowned sparrow (Zonotrichia atricapilla) and the white-crowned sparrow (Zonotrichia leucophrys) are phenotypically differentiated sister species that are largely reproductively isolated despite possessing similar mitochondrial genomes, likely due to recent introgression. We assessed variation in more than 45,000 single nucleotide polymorphisms to determine the structure of nuclear genomic differentiation between these species and between two hybridizing subspecies of Z. leucophrys. The two Z. leucophrys subspecies show moderate levels of relative differentiation and patterns consistent with a history of recurrent selection in both ancestral and daughter populations, with much of the sex chromosome Z and a large region on the autosome 1A showing increased differentiation compared to the rest of the genome. The two species Z. leucophrys and Z. atricapilla show high relative differentiation and strong heterogeneity in the level of differentiation among various chromosomal regions, with a large portion of the sex chromosome (Z) showing highly divergent haplotypes between these species. Studies of speciation often emphasize mitochondrial DNA differentiation, but speciation between Z. atricapilla and Z. leucophrys appears primarily associated with Z chromosome divergence and more moderately associated with autosomal differentiation, whereas mitochondria are highly similar due apparently to recent introgression. These results add to the growing body of evidence for highly heterogeneous patterns of genomic differentiation during speciation, with some genomic regions showing a lack of gene flow between populations many hundreds of thousands of years before other genomic regions.

RevDate: 2024-02-01
CmpDate: 2024-02-01

Yordanov G, Palova N, Mehandjyiski I, et al (2023)

Mitochondrial DNA sequencing illuminates genetic diversity and origin of Hunagrian Nonius horse breed and his relatives - Danubian horse and Serbian Nonius.

Animal biotechnology, 34(8):3897-3907.

From a historical perspective, horse breeding in Bulgaria has been very well developed since the time of the Thracians (early Bronze Age c. 3000 BCE). Archaeological discoveries from this era present us with an extremely rich type diversity, including wild and local primitive horses, the prototype of heavy draft horses, and fine riding horses.The objective of this study was to investigate the genetic structure of unexamined populations of three closely related horse breeds - the Danubian Nonius Hungarian Nonius and Serbian Nonius horses. A 608 bp long fragment of the mtDNA D-loop region was amplified and sequenced. The obtained results showed completely different genetic profiles between the investigated breeds. We identified nine of the 17 haplogroups described in modern horses. Most of the obtained sequences fell into M, L, G, and O'P lineages, which reflects the genetic profiles of the ancestral mares that were probably used at the initial stages of formation of the breeds. The population of the Danubian horse was characterized by a high prevalence of Central Asian specific haplogroup G (45%), followed by Western Eurasian specific haplogroups L and M (both about 21%). In contrast to the Danubian horse, in the Nonius breed the highest frequency of Western Eurasian haplogroup M (43.5%) was found, followed by Middle Eastern haplogroups O'P (26.1%) Central Asian specific E (13.0%) and G (13.1%). The Serbian Nonius horse showed a completely different genetic profile with a prevalence of the rare for Europe haplogroup D (66.7%), followed by Central Asian specific G (16.7%). The high mitochondrial haplotype diversity (Hd = 0.886) found in the investigated samples is evidence for multiple maternal origins in all populations.In conclusion, the obtained results demonstrated a high percentage of haplogroup sharing especially in the Danubian and Hungarian Nonius horse breeds, which reflects the possible common origins of the two breeds. In contrast to these breeds, the Serbian Nonius, despite the small number of investigated animals, showed a specific genetic profile, which could be explained by different and independent origins.

RevDate: 2024-01-31
CmpDate: 2024-01-31

Chen S, Tran TTT, Yeh AY, et al (2024)

The Globodera rostochiensis Gr29D09 Effector with a Role in Defense Suppression Targets the Potato Hexokinase 1 Protein.

Molecular plant-microbe interactions : MPMI, 37(1):25-35.

The potato cyst nematode (Globodera rostochiensis) is an obligate root pathogen of potatoes. G. rostochiensis encodes several highly expanded effector gene families, including the Gr4D06 family; however, little is known about the function of this effector family. We cloned four 29D09 genes from G. rostochiensis (named Gr29D09v1/v2/v3/v4) that share high sequence similarity and are homologous to the Hg29D09 and Hg4D06 effector genes from the soybean cyst nematode (Heterodera glycines). Phylogenetic analysis revealed that Gr29D09 genes belong to a subgroup of the Gr4D06 family. We showed that Gr29D09 genes are expressed exclusively within the nematode's dorsal gland cell and are dramatically upregulated in parasitic stages, indicating involvement of Gr29D09 effectors in nematode parasitism. Transgenic potato lines overexpressing Gr29D09 variants showed increased susceptibility to G. rostochiensis. Transient expression assays in Nicotiana benthamiana demonstrated that Gr29D09v3 could suppress reactive oxygen species (ROS) production and defense gene expression induced by flg22 and cell death mediated by immune receptors. These results suggest a critical role of Gr29D09 effectors in defense suppression. The use of affinity purification coupled with nanoliquid chromatography-tandem mass spectrometry identified potato hexokinase 1 (StHXK1) as a candidate target of Gr29D09. The Gr29D09-StHXK1 interaction was further confirmed using in planta protein-protein interaction assays. Plant HXKs have been implicated in defense regulation against pathogen infection. Interestingly, we found that StHXK1 could enhance flg22-induced ROS production, consistent with a positive role of plant HXKs in defense. Altogether, our results suggest that targeting StHXK1 by Gr29D09 effectors may impair the positive function of StHXK1 in plant immunity, thereby aiding nematode parasitism. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

RevDate: 2024-01-30

Li X, Zhu Y, Ruiz-Lozano P, et al (2024)

Mitochondrial-to-nuclear communications through multiple routes regulate cardiomyocyte proliferation.

Cell regeneration (London, England), 13(1):2.

The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research. Despite extensive investigations into the loss of regenerative potential during evolution and development, unlocking the mechanisms governing cardiomyocyte proliferation remains elusive. Two recent groundbreaking studies have provided fresh perspectives on mitochondrial-to-nuclear communication, shedding light on novel factors that regulate cardiomyocyte proliferation. The studies identified two mitochondrial processes, fatty acid oxidation and protein translation, as key players in restricting cardiomyocyte proliferation. Inhibition of these processes led to increased cell cycle activity in cardiomyocytes, mediated by reduction in H3k4me3 levels through accumulated α-ketoglutarate (αKG), and activation of the mitochondrial unfolded protein response (UPR[mt]), respectively. In this research highlight, we discuss the novel insights into mitochondrial-to-nuclear communication presented in these studies, the broad implications in cardiomyocyte biology and cardiovascular diseases, as well as the intriguing scientific questions inspired by the studies that may facilitate future investigations into the detailed molecular mechanisms of cardiomyocyte metabolism, proliferation, and mitochondrial-to-nuclear communications.

RevDate: 2024-01-30

Cao J, Luo Y, Chen Y, et al (2024)

Maternal mitochondrial function affects paternal mitochondrial inheritance in Drosophila.

Genetics pii:7593495 [Epub ahead of print].

The maternal inheritance of mitochondria is a widely accepted paradigm, and mechanisms that prevent paternal mitochondria transmission to offspring during spermatogenesis and post-fertilization have been described. Although certain species do retain paternal mitochondria, the factors affecting paternal mitochondria inheritance in these cases are unclear. More importantly, the evolutionary benefit of retaining paternal mitochondria and their ultimate fate are unknown. Here we show that transplanted exogenous paternal D. yakuba mitochondria can be transmitted to offspring when maternal mitochondria are dysfunctional in D. melanogaster. Furthermore, we show that the preserved paternal mitochondria are functional, and can be stably inherited, such that the proportion of paternal mitochondria increases gradually in subsequent generations. Our work has important implications that paternal mitochondria inheritance should not be overlooked as a genetic phenomenon in evolution, especially when paternal mitochondria are of significant differences from the maternal mitochondria or the maternal mitochondria are functionally abnormal. Our results improve the understanding of mitochondrial inheritance and provide a new model system for its study.

RevDate: 2024-01-30

Meng X, Wang D, Pang Q, et al (2024)

Multiple independent origins of duplicated mitochondrial control regions indicate an apomorphy in the Thysanoptera (Insecta).

Archives of insect biochemistry and physiology, 115(1):e22087.

The mitochondrial genome (mitogenome) of thrips is characterized by the presence of control region (CR) duplication. However, the evolution pattern of duplicated CRs in thrips is still unclear. In this study, the multiple independent origins of duplicated CR indicated that the CR duplication was not an ancestral state for Thysanoptera. The macroevolutionary pattern suggested that the earliest CR duplication event occurred in the middle Cretaceous (94.85 Ma) coincided with rearrangement events forming the ancestors of Aeolothripidae, but much later than that forming the ancestors of the suborder Terebrantia. The mitogenome with duplicated CRs showed a higher rate of gene rearrangement. The sequence similarity of the CR copies and divergence time were negatively correlated, indicating age-related deterioration of mitochondrial function. No significant differences were found in the mitochondrial DNA, the P123 and P4FD between the single and multiple-CR charactered mitogenomes, which suggested that the duplicated CRs may not affect the replication process in thrip mitogenome. The mitogenomes with duplicated CRs (mean: 0.0088 subs/s/my) show a significantly increased evolutionary rate than that with a single one (mean: 0.0058 subs/s/my). However, it seems that this higher evolutionary rate did not have adaptive mechanisms in Terebrantia. We speculated that the duplicated CRs may cause a more intense production of energy by mitochondria, and an accelerated mutation and substitution rate is expected in such mitogenomes. Our study provided new insights into the presence of CR duplications and their evolution in the mitogenomes of thrips.

RevDate: 2024-01-29
CmpDate: 2024-01-29

Li K, Yu SW, Hu H, et al (2023)

The Phylogenetic Relationship of Lamiinae (Coleoptera: Cerambycidae) Using Mitochondrial Genomes.

Genes, 15(1):.

Lamiinae is the largest subfamily of the Cerambycidae (longhorn beetles), with approximately 21,863 described species. Previous phylogenetic studies of Lamiinae showed that this subfamily was monophyletic, but the relationship between the tribes of Lamiinae is still controversial. Partial molecular data and species morphological characteristics are not sufficient to resolve species phylogenetic studies perfectly. At the same time, the full mitochondrial genome contains more comprehensive genetic data. Benefiting from the development of next-generation sequencing (NGS), mitochondrial genomes can be easily acquired and used as reliable molecular markers to investigate phylogenetic relationships within Cerambycidae. Using NGS technology, we obtained 11 mitochondrial genome sequences of Lamiinae species. Based on this newly generated mitochondrial genome dataset matrix, we reconstructed the phylogeny of Lamiinae. The Bayesian Inference and Maximum Likelihood analyses strongly support the monophyly of four tribes (Lamiini, Batocerini, Mesosini, and Saperdini), whereas the tribe Acanthocinini was identified as paraphyletic. Other mitochondrial structural features were also observed: the start codon in the nad1 gene of all 11 mitochondrial genomes is TTG; 17-22 bp intergenic spacers (IGS) with a 'TACTA' motif were found between trnS2 and nad1. Moreover, two long IGS were found in Mesosa myops and Batocera sp. Tandem repeats were found in the IGS of Batocera sp.

RevDate: 2024-01-29
CmpDate: 2024-01-29

Bian C, Ji S, Xue R, et al (2024)

Molecular cloning and characterization of BNIP3 and NIX1/2 and their role in DHA-induced mitophagy and apoptosis in grass carp (Ctenopharyngodon idellus) adipocytes.

Gene, 899:148140.

B-cell lymphoma-2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) and BNIP3 like (BNIP3L or NIX) play a vital role in regulating mitophagy and the intrinsic apoptosis in mammals, but their gene characterizations remain unclear in fish. Herein, bnip3, nix1 and nix2 were isolated and characterized from grass carp (Ctenopharyngodon idellus), which encode peptides of 194, 233 and 222 amino acids, respectively. As typical BH3-only proteins, grass carp BNIP3, NIX1 and NIX2 proteins contain BH3 and C-terminal transmembrane domains for inducing apoptosis. Moreover, the LC3-interacting region motif of BNIP3, NIX1 and NIX2 is also conserved in grass carp. Phylogenetic analyses also demonstrated that nix1 and nix2 may have originated from the genome duplication event. Expression pattern analysis indicated that bnip3, nix1 and nix2 were highest expressed in brain, followed by eye (bnip3) and liver (nix1 and nix2). BNIP3, NIX1 and NIX2 localized to the nucleus and the cytoplasm, with a predominant localization to mitochondria within the cytoplasm. In the present study, we found that 200 μM DHA impaired the mitochondrial function, manifested as the decreased antioxidant ability, cellular ATP content and mitochondrial membrane potential in grass carp adipocytes. In addition, the gene expression and enzyme activities of caspase family were significantly increased in 200 μM DHA group, indicating that adipocyte apoptosis was induced. Meanwhile, DHA increased the gene expression of bnip3, nix1 and nix2 in a dose-dependent manner in grass carp adipocytes. The colocalization of mitochondria and lysosomes was promoted by 200 μM DHA treatment, implying that BNIP3/NIX-related mitophagy was activated in adipocytes. Based on these findings, it can be inferred that BNIP3/NIX-related mitophagy may be involved in the adipocyte apoptosis induced by DHA in grass carp.

RevDate: 2024-01-25

Butenko A, Lukeš J, Speijer D, et al (2024)

Mitochondrial genomes revisited: why do different lineages retain different genes?.

BMC biology, 22(1):15.

The mitochondria contain their own genome derived from an alphaproteobacterial endosymbiont. From thousands of protein-coding genes originally encoded by their ancestor, only between 1 and about 70 are encoded on extant mitochondrial genomes (mitogenomes). Thanks to a dramatically increasing number of sequenced and annotated mitogenomes a coherent picture of why some genes were lost, or relocated to the nucleus, is emerging. In this review, we describe the characteristics of mitochondria-to-nucleus gene transfer and the resulting varied content of mitogenomes across eukaryotes. We introduce a 'burst-upon-drift' model to best explain nuclear-mitochondrial population genetics with flares of transfer due to genetic drift.

RevDate: 2024-01-25

Serrano MJ, Goudet J, T Cumer (2024)

Characterization of the diversity of barn owl's mitochondrial genome reveals high copy number variations in the control region.

PloS one, 19(1):e0295595 pii:PONE-D-23-20889.

Mitochondria are known to play an essential role in the cell. These organelles contain their own DNA, which is divided in a coding and non-coding region (NCR). While much of the NCR's function is unknown, tandem repeats have been observed in several vertebrates, with extreme intra-individual, intraspecific and interspecific variation. Taking advantage of a new complete reference for the mitochondrial genome of the Afro-European Barn Owl (Tyto alba), as well as 172 whole genome-resequencing; we (i) describe the reference mitochondrial genome with a special focus on the repeats in the NCR, (ii) quantify the variation in number of copies between individuals, and (iii) explore the possible factors associated with the variation in the number of repetitions. The reference mitochondrial genome revealed a long (256bp) and a short (80bp) tandem repeat in the NCR region. The re-sequenced genomes showed a great variation in number of copies between individuals, with 4 to 38 copies of the Long and 6 to 135 copies of the short repeat. Among the factors associated with this variation between individuals, the tissue used for extraction was the most significant. The exact mechanisms of the formations of these repeats are still to be discovered and understanding them will help explain the maintenance of the polymorphism in the number of copies, as well as their interactions with the metabolism, the aging and health of the individuals.

RevDate: 2024-01-25

Harada R, Hirakawa Y, Yabuki A, et al (2024)

Encyclopaedia of family A DNA polymerases localized in organelles: Evolutionary contribution of bacteria including the proto-mitochondrion.

Molecular biology and evolution pii:7589574 [Epub ahead of print].

DNA polymerases (DNAPs) synthesize DNA from deoxyribonucleotides in a semi-conservative manner and serve as the core of DNA replication and repair machineries. In eukaryotic cells, there are two genome-containing organelles, mitochondria and plastids, that were derived from an alphaproteobacterium and a cyanobacterium, respectively. Except for rare cases of genome-lacking mitochondria and plastids, both organelles must be served by nucleus-encoded DNAPs that localize and work in them to maintain their genomes. The evolution of organellar DNAPs has yet to be fully understood because of two unsettled issues. First, the diversity of organellar DNAPs has not been elucidated in the full spectrum of eukaryotes. Second, it is unclear when the DNAPs that were used originally in the endosymbiotic bacteria giving rise to mitochondria and plastids were discarded, as the organellar DNAPs known to date show no phylogenetic affinity to those of the extant alphaproteobacteria or cyanobacteria. In this study, we identified from diverse eukaryotes 134 family A DNAP sequences, which were classified into 10 novel types, and explored their evolutionary origins. The subcellular localizations of selected DNAPs were further examined experimentally. The results presented here suggest that the diversity of organellar DNAPs has been shaped by multiple transfers of the PolI gene from phylogenetically broad bacteria, and their occurrence in eukaryotes was additionally impacted by secondary plastid endosymbioses. Finally, we propose that the last eukaryotic common ancestor may have possessed two mitochondrial DNAPs, POP and a candidate of the direct descendant of the proto-mitochondrial DNAP, rdxPolA, identified in this study.

RevDate: 2024-01-24

Takusagawa M, Misumi O, Nozaki H, et al (2024)

Complete mitochondrial and chloroplast DNA sequences of the freshwater green microalga Medakamo hakoo.

Genes & genetic systems [Epub ahead of print].

We report the complete organellar genome sequences of an ultrasmall green alga, Medakamo hakoo strain M-hakoo 311, which has the smallest known nuclear genome in freshwater green algae. Medakamo hakoo has 90.8-kb chloroplast and 36.5-kb mitochondrial genomes containing 80 and 33 putative protein-coding genes, respectively. The mitochondrial genome is the smallest in the Trebouxiophyceae algae studied so far. The GC content of the nuclear genome is 73%, but those of chloroplast and mitochondrial genomes are 41% and 35%, respectively. Codon usages in the organellar genomes have a different tendency from that in the nuclear genome. The organellar genomes have unique characteristics, such as the biased encoding of mitochondrial genes on a single strand and the absence of operon structures in chloroplast ribosomal genes. Medakamo hakoo will be helpful for understanding the evolution of the organellar genome and the regulation of gene expression in chloroplasts and mitochondria.

RevDate: 2024-01-24
CmpDate: 2024-01-24

Li X, Li W, Huo J, et al (2024)

[Identification and expression analysis of citrate synthase 3 gene family members in apple].

Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 40(1):137-149.

As one of the key enzymes in cell metabolism, the activity of citrate synthase 3 (CS3) regulates the substance and energy metabolism of organisms. The protein members of CS3 family were identified from the whole genome of apple, and bioinformatics analysis was performed and expression patterns were analyzed to provide a theoretical basis for studying the potential function of CS3 gene in apple. BLASTp was used to identify members of the apple CS3 family based on the GDR database, and the basic information of CS3 protein sequence, subcellular localization, domain composition, phylogenetic relationship and chromosome localization were analyzed by Pfam, SMART, MEGA5.0, clustalx.exe, ExPASy Proteomics Server, MEGAX, SOPMA, MEME, WoLF PSORT and other software. The tissue expression and inducible expression characteristics of 6 CS3 genes in apple were determined by acid content and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Apple CS3 gene family contains 6 members, and these CS3 proteins contain 473-608 amino acid residues, with isoelectric point distribution between 7.21 and 8.82. Subcellular localization results showed that CS3 protein was located in mitochondria and chloroplasts, respectively. Phylogenetic analysis divided them into 3 categories, and the number of genes in each subfamily was 2. Chromosome localization analysis showed that CS3 gene was distributed on different chromosomes of apple. The secondary structure of protein is mainly α-helix, followed by random curling, and the proportion of β-angle is the smallest. The 6 members were all expressed in different apple tissues. The overall expression trend from high to low was the highest relative expression content of MdCS3.4, followed by MdCS3.6, and the relative expression level of other members was in the order of MdCS3.3 > MdCS3.2 > MdCS3.1 > MdCS3.5. qRT-PCR results showed that MdCS3.1 and MdCS3.3 genes had the highest relative expression in the pulp of 'Chengji No. 1' with low acid content, and MdCS3.2 and MdCS3.3 genes in the pulp of 'Asda' with higher acid content had the highest relative expression. Therefore, in this study, the relative expression of CS3 gene in apple cultivars with different acid content in different apple varieties was detected, and its role in apple fruit acid synthesis was analyzed. The experimental results showed that the relative expression of CS3 gene in different apple varieties was different, which provided a reference for the subsequent study of the quality formation mechanism of apple.

RevDate: 2024-01-23

Tang W, Li X, Ye B, et al (2024)

Characterization of the complete mitochondrial genome and phylogenetic analyses of Haemaphysalis tibetensis Hoogstraal, 1965 (Acari: Ixodidae).

Ticks and tick-borne diseases, 15(2):102311 pii:S1877-959X(24)00004-9 [Epub ahead of print].

Ticks are specialized ectoparasites that feed on blood, causing physical harm to the host and facilitating pathogen transmission. The genus Haemaphysalis contains vectors for numerous infectious agents. These agents cause various diseases in humans and animals. Mitochondrial genome sequences serve as reliable molecular markers, forming a crucial basis for evolutionary analyses, studying species origins, and exploring molecular phylogeny. We extracted mitochondrial genome from the enriched mitochondria of Haemaphysalis tibetensis and obtained a 14,714-bp sequence. The mitochondrial genome consists of 13 protein-coding genes (PCGs), two ribosomal RNA, 22 transfer RNAs (tRNAs), and two control regions. The nucleotide composition of H. tibetensis mitochondrial genome was 38.38 % for A, 9.61 % for G, 39.32 % for T, and 12.69 % for C. The A + T content of H. tibetensis mitochondrial genome was 77.7 %, significantly higher than the G + C content. The repeat units of H. tibetensis exhibited two identical repeat units of 33 bp in length, positioned downstream of nad1 and rrnL genes. Furthermore, phylogenetic analyses based on the 13 PCGs indicated that Haemaphysalis tibetensis (subgenus Allophysalis) formed a monophyletic clade with Haemaphysalis nepalensis (subgenus Herpetobia) and Haemaphysalis danieli (subgenus Allophysalis). Although the species Haemaphysalis inermis, Haemaphysalis kitaokai, Haemaphysalis kolonini, and Haemaphysalis colasbelcouri belong to the subgenus Alloceraea, which were morphologically primitive hemaphysalines just like H. tibetensis, these four tick species cannot form a single clade with H. tibetensis. In this study, the whole mitochondrial genome sequence of H. tibetensis from Tibet was obtained, which enriched the mitochondrial genome data of ticks and provided genetic markers to study the population heredity and molecular evolution of the genus Haemaphysalis.

RevDate: 2024-01-23

Eglit Y, Shiratori T, Jerlström-Hultqvist J, et al (2024)

Meteora sporadica, a protist with incredible cell architecture, is related to Hemimastigophora.

Current biology : CB, 34(2):451-459.e6.

"Kingdom-level" branches are being added to the tree of eukaryotes at a rate approaching one per year, with no signs of slowing down.[1][,][2][,][3][,][4] Some are completely new discoveries, whereas others are morphologically unusual protists that were previously described but lacked molecular data. For example, Hemimastigophora are predatory protists with two rows of flagella that were known since the 19[th] century but proved to represent a new deep-branching eukaryote lineage when phylogenomic analyses were conducted.[2]Meteora sporadica[5] is a protist with a unique morphology; cells glide over substrates along a long axis of anterior and posterior projections while a pair of lateral "arms" swing back and forth, a motility system without any obvious parallels. Originally, Meteora was described by light microscopy only, from a short-term enrichment of deep-sea sediment. A small subunit ribosomal RNA (SSU rRNA) sequence was reported recently, but the phylogenetic placement of Meteora remained unresolved.[6] Here, we investigated two cultivated Meteora sporadica isolates in detail. Transmission electron microscopy showed that both the anterior-posterior projections and the arms are supported by microtubules originating from a cluster of subnuclear microtubule organizing centers (MTOCs). Neither have a flagellar axoneme-like structure. Sequencing the mitochondrial genome showed this to be among the most gene-rich known, outside jakobids. Remarkably, phylogenomic analyses of 254 nuclear protein-coding genes robustly support a close relationship with Hemimastigophora. Our study suggests that Meteora and Hemimastigophora together represent a morphologically diverse "supergroup" and thus are important for resolving the tree of eukaryote life and early eukaryote evolution.

RevDate: 2024-01-23

Sequeira AN, O'Keefe IP, Katju V, et al (2024)

Friend turned foe: selfish behavior of a spontaneously arising mitochondrial deletion in an experimentally evolved C. elegans population.

G3 (Bethesda, Md.) pii:7585480 [Epub ahead of print].

Selfish mitochondrial DNA (mtDNA) mutations are variants that can proliferate within cells and enjoy a replication or transmission bias without fitness benefits for the host. MtDNA deletions in Caenorhabditis elegans can reach high heteroplasmic frequencies despite significantly reducing fitness, illustrating how new mtDNA variants can give rise to genetic conflict between different levels of selection, and between the nuclear and mitochondrial genomes. During a mutation accumulation (MA) experiment in C. elegans, a 1,034 bp deletion originated spontaneously and reached an 81.7% frequency within an experimental evolution line. This heteroplasmic mtDNA deletion, designated as meuDf1, eliminated portions of two protein-coding genes (coxIII and nd4) and tRNA-thr in entirety. MtDNA copy-number in meuDf1 heteroplasmic individuals was 35% higher than in individuals with wildtype mitochondria. After backcrossing into a common genetic background, the meuDf1 mitotype was associated with reduction in several fitness traits and independent competition experiments found a 40% reduction in composite fitness. Experiments that relaxed individual selection by single individual bottlenecks demonstrated that the deletion-bearing mtDNA possessed a strong transmission bias, thereby qualifying it as a novel selfish mitotype.

RevDate: 2024-01-23

Zhang Y, Li H, Wang Y, et al (2024)

Mitogenomic architecture and evolution of the soil ciliates Colpoda.

mSystems [Epub ahead of print].

Colpoda are cosmopolitan unicellular eukaryotes primarily inhabiting soil and benefiting plant growth, but they remain one of the least understood taxa in genetics and genomics within the realm of ciliated protozoa. Here, we investigate the architecture of de novo assembled mitogenomes of six Colpoda species, using long-read sequencing and involving 36 newly isolated natural strains in total. The mitogenome sizes span from 43 to 63 kbp and typically contain 28-33 protein-coding genes. They possess a linear structure with variable telomeres and central repeats, with one Colpoda elliotti strain isolated from Tibet harboring the longest telomeres among all studied ciliates. Phylogenomic analyses reveal that Colpoda species started to diverge more than 326 million years ago, eventually evolving into two distinct groups. Collinearity analyses also reveal significant genomic divergences and a lack of long collinear blocks. One of the most notable features is the exceptionally high level of gene rearrangements between mitochondrial genomes of different Colpoda species, dominated by gene loss events. Population-level mitogenomic analysis on natural strains also demonstrates high sequence divergence, regardless of geographic distance, but the gene order remains highly conserved within species, offering a new species identification criterion for Colpoda species. Furthermore, we identified underlying heteroplasmic sites in the majority of strains of three Colpoda species, albeit without a discernible recombination signal to account for this heteroplasmy. This comprehensive study systematically unveils the mitogenomic structure and evolution of these ancient and ecologically significant Colpoda ciliates, thus laying the groundwork for a deeper understanding of the evolution of unicellular eukaryotes.IMPORTANCEColpoda, one of the most widespread ciliated protozoa in soil, are poorly understood in regard to their genetics and evolution. Our research revealed extreme mitochondrial gene rearrangements dominated by gene loss events, potentially leading to the streamlining of Colpoda mitogenomes. Surprisingly, while interspecific rearrangements abound, our population-level mitogenomic study revealed a conserved gene order within species, offering a potential new identification criterion. Phylogenomic analysis traced their lineage over 326 million years, revealing two distinct groups. Substantial genomic divergence might be associated with the lack of extended collinear blocks and relaxed purifying selection. This study systematically reveals Colpoda ciliate mitogenome structures and evolution, providing insights into the survival and evolution of these vital soil microorganisms.

RevDate: 2024-01-23

Mirra S, G Marfany (2024)

From Beach to the Bedside: Harnessing Mitochondrial Function in Human Diseases Using New Marine-Derived Strategies.

International journal of molecular sciences, 25(2): pii:ijms25020834.

Mitochondria are double-membrane organelles within eukaryotic cells that act as cellular power houses owing to their ability to efficiently generate the ATP required to sustain normal cell function. Also, they represent a "hub" for the regulation of a plethora of processes, including cellular homeostasis, metabolism, the defense against oxidative stress, and cell death. Mitochondrial dysfunctions are associated with a wide range of human diseases with complex pathologies, including metabolic diseases, neurodegenerative disorders, and cancer. Therefore, regulating dysfunctional mitochondria represents a pivotal therapeutic opportunity in biomedicine. Marine ecosystems are biologically very diversified and harbor a broad range of organisms, providing both novel bioactive substances and molecules with meaningful biomedical and pharmacological applications. Recently, many mitochondria-targeting marine-derived molecules have been described to regulate mitochondrial biology, thus exerting therapeutic effects by inhibiting mitochondrial abnormalities, both in vitro and in vivo, through different mechanisms of action. Here, we review different strategies that are derived from marine organisms which modulate specific mitochondrial processes or mitochondrial molecular pathways and ultimately aim to find key molecules to treat a wide range of human diseases characterized by impaired mitochondrial function.

RevDate: 2024-01-22
CmpDate: 2024-01-22

Seesamut T, Oba Y, Jirapatrasilp P, et al (2024)

Global species delimitation of the cosmopolitan marine littoral earthworm Pontodrilus litoralis (Grube, 1855).

Scientific reports, 14(1):1753.

The marine littoral earthworm Pontodrilus litoralis (Grube, 1855) is widely distributed and is reported as a single species. This study utilized an integrative taxonomic approach based upon morphological examination, phylogenetic reconstruction, and molecular species delimitation, to test whether the taxon is a single species or a species complex. For this, a total of 114 P. litoralis specimens collected from North America, Africa, Australia and Oceania, Europe and Asia were used. The phylogenetic analyses revealed deeply divergent mitochondrial lineages and a high level of genetic diversity among P. litoralis populations. Both single and multi-locus species delimitation analyses yielded several molecular operational taxonomic units. Therefore, due to the homogeneity of morphological characteristics, it is likely that the morphospecies P. litoralis is a complex of four or more cryptic species, suggesting that more sampling is required and that the population structure genetic data and gene flow need to be investigated.

RevDate: 2024-01-22
CmpDate: 2024-01-22

Choi SW, Yu HJ, JK Kim (2024)

Comparative ontogeny and phylogenetic relationships of eight lizardfish species (Synodontidae) from the Northwest Pacific, with a focus on Trachinocephalus monophyly.

Journal of fish biology, 104(1):284-303.

Lizardfish (Aulopiforms: Synodontidae), distributed broadly in temperate to tropical waters, are represented globally by 83 species across four genera, with 10 species in Korea. Despite these numbers, few studies have been conducted on the early life history of lizardfishes compared to their adult counterparts. Thus, we conducted molecular identification of 123 Synodontidae larvae collected from the Northwest Pacific (Korea Strait, Yellow Sea, East China Sea, and East Sea) between June 2017 and July 2021, using mitochondrial DNA COI and 16S rRNA sequences. Significant morphological differences were observed in the larvae and juvenile, including variation in melanophore, count, morphometric characteristics, and body shape. The morphological traits of eight species (Harpadon nehereus, Saurida macrolepis, Saurida wanieso, Saurida sp., Synodus hoshinonis, Synodus kaianus, Synodus macrops, and Trachinocephalus trachinus) served as vital data for interpreting the phylogenetic relationships within the Northwest Pacific Synodontidae. Ultimately, the identification key revealed by this study will enable accurate identification of Synodontid larvae and juveniles, and further facilitate our understanding of the phylogenetic relationships within this family.

RevDate: 2024-01-19

Satoh S, Miyake K, Adachi Y, et al (2024)

Cancer-associated SNRPD3 mutation confers resistance to hypoxia, which is attenuated by DRP1 inhibition.

Biochemical and biophysical research communications, 696:149511 pii:S0006-291X(24)00046-9 [Epub ahead of print].

RNA splicing is a fundamental cellular mechanism performed by spliceosomes that synthesise multiple mature RNA isoforms from a single gene. The association between spliceosome abnormality and solid cancers remains largely unknown. Here, we demonstrated that Sm proteins, which are common components of the spliceosomes and constitute the Sm ring, were overexpressed in multiple cancers and their expression levels were correlated with clinical prognosis. In a pan-cancer mutational hotspot in the Sm ring at SNRPD3 G96V, we found that the G96V substitution confers resistance to hypoxia. RNA-seq detected numerous differentially spliced events between the wild-type and mutation-carrying cells cultured under hypoxia, wherein skipping exons and mutually exclusive exons were frequently observed. This was observed in DNM1L mRNA, which encodes the DRP1 protein that regulates mitochondrial fission. The mitochondria of cells carrying this mutation were excessively fragmented compared with those of wild-type cells. Furthermore, treatment with a DRP1 inhibitor (Mdivi-1) recovered the over-fragmented mitochondria, leading to the attenuation of hypoxia resistance in the mutant cells. These results propose a novel correlation between the cancer-related spliceosome abnormality and mitochondrial fission. Thus, targeting SNRPD3 G96V with a DRP1 inhibitor is a potential treatment strategy for cancers with spliceosome abnormalities.

RevDate: 2024-01-18

Ali NA, Song W, Huang J, et al (2024)

Recent advances and biotechnological applications of RNA metabolism in plant chloroplasts and mitochondria.

Critical reviews in biotechnology [Epub ahead of print].

The chloroplast and mitochondrion are semi-autonomous organelles that play essential roles in cell function. These two organelles are embellished with prokaryotic remnants and contain many new features emerging from the co-evolution of organelles and the nucleus. A typical plant chloroplast or mitochondrion genome encodes less than 100 genes, and the regulation of these genes' expression is remarkably complex. The regulation of chloroplast and mitochondrion gene expression can be achieved at multiple levels during development and in response to environmental cues, in which, RNA metabolism, including: RNA transcription, processing, translation, and degradation, plays an important role. RNA metabolism in plant chloroplasts and mitochondria combines bacterial-like traits with novel features evolved in the host cell and is regulated by a large number of nucleus-encoded proteins. Among these, pentatricopeptide repeat (PPR) proteins are deeply involved in multiple aspects of the RNA metabolism of organellar genes. Research over the past decades has revealed new insights into different RNA metabolic events in plant organelles, such as the composition of chloroplast and mitochondrion RNA editosomes. We summarize and discuss the most recent knowledge and biotechnological implications of various RNA metabolism processes in plant chloroplasts and mitochondria, with a focus on the nucleus-encoded factors supporting them, to gain a deeper understanding of the function and evolution of these two organelles in plant cells. Furthermore, a better understanding of the role of nucleus-encoded factors in chloroplast and mitochondrion RNA metabolism will motivate future studies on manipulating the plant gene expression machinery with engineered nucleus-encoded factors.

RevDate: 2024-01-18

Bayazit MB, Francois A, McGrail E, et al (2023)

mt-tRNAs in the polymerase gamma mutant heart.

The journal of cardiovascular aging, 3(4):.

INTRODUCTION: Mice harboring a D257A mutation in the proofreading domain of the mitochondrial DNA polymerase, Polymerase Gamma (POLG), experience severe metabolic dysfunction and display hallmarks of accelerated aging. We previously reported a mitochondrial unfolded protein response (UPT[mt]) - like (UPR[mt]-like) gene and protein expression pattern in the right ventricular tissue of POLG mutant mice.

AIM: We sought to determine if POLG mutation altered the expression of genes encoded by the mitochondria in a way that might also reduce proteotoxic stress.

METHODS AND RESULTS: The expression of genes encoded by the mitochondrial DNA was interrogated via RNA-seq and northern blot analysis. A striking, location-dependent effect was seen in the expression of mitochondrial-encoded tRNAs in the POLG mutant as assayed by RNA-seq. These expression changes were negatively correlated with the tRNA partner amino acid's amyloidogenic potential. Direct measurement by northern blot was conducted on candidate mt-tRNAs identified from the RNA-seq. This analysis confirmed reduced expression of MT-TY in the POLG mutant but failed to show increased expression of MT-TP, which was dramatically increased in the RNA-seq data.

CONCLUSION: We conclude that reduced expression of amyloid-associated mt-tRNAs is another indication of adaptive response to severe mitochondrial dysfunction in the POLG mutant. Incongruence between RNA-seq and northern blot measurement of MT-TP expression points towards the existence of mt-tRNA post-transcriptional modification regulation in the POLG mutant that alters either polyA capture or cDNA synthesis in RNA-seq library generation. Together, these data suggest that 1) evolution has distributed mt-tRNAs across the circular mitochondrial genome to allow chromosomal location-dependent mt-tRNA regulation (either by expression or PTM) and 2) this regulation is cognizant of the tRNA partner amino acid's amyloidogenic properties.

RevDate: 2024-01-16

Krishnan N, Csiszár V, Móri TF, et al (2024)

Genesis of ectosymbiotic features based on commensalistic syntrophy.

Scientific reports, 14(1):1366.

The symbiogenetic origin of eukaryotes with mitochondria is considered a major evolutionary transition. The initial interactions and conditions of symbiosis, along with the phylogenetic affinity of the host, are widely debated. Here, we focus on a possible evolutionary path toward an association of individuals of two species based on unidirectional syntrophy. With the backing of a theoretical model, we hypothesize that the first step in the evolution of such symbiosis could be the appearance of a linking structure on the symbiont's membrane, using which it forms an ectocommensalism with its host. We consider a commensalistic model based on the syntrophy hypothesis in the framework of coevolutionary dynamics and mutant invasion into a monomorphic resident system (evolutionary substitution). We investigate the ecological and evolutionary stability of the consortium (or symbiotic merger), with vertical transmissions playing a crucial role. The impact of the 'effectiveness of vertical transmission' on the dynamics is also analyzed. We find that the transmission of symbionts and the additional costs incurred by the mutant determine the conditions of fixation of the consortia. Additionally, we observe that small and highly metabolically active symbionts are likely to form the consortia.

RevDate: 2024-01-16
CmpDate: 2024-01-16

Doniol-Valcroze P, Coiffard P, Alstrm P, et al (2023)

Molecular and acoustic evidence support the species status of Anthus rubescens rubescens and Anthus [rubescens] japonicus (Passeriformes: Motacillidae).

Zootaxa, 5343(2):173-192.

The Buff-bellied Pipit Anthus rubescens comprises two allopatric subspecies groups: A. r. rubescens and A. r. alticola in North America and A. [r.] japonicus in north-east Asia. Despite their great morphological resemblance in breeding plumage, most individuals can be assigned to one or the other subspecies group in non-breeding plumage. Allopatric distributions, morphological differentiation and previously reported molecular divergence suggested the need for additional taxonomic study to assess the rank of these two populations. To resolve the taxonomy of the Buff-bellied Pipit species complex we analysed i) two mitochondrial DNA (mtDNA) loci and ii) nine bioacoustic parameters across 69 sound recordings (338 flight calls) recovered from public databases using principal component analysis and Euclidean distance measures. By comparing our mtDNA and call divergence measures with similar values measured between long-recognised species pairs of the genus, we show that the level of mitochondrial and acoustic divergence between the two Buff-bellied Pipit subspecies groups is typical of species-level divergence in the genus Anthus. Therefore, we recommend splitting the Buff-bellied Pipit species complex into two species: Anthus rubescens (American Pipit) and Anthus japonicus (Siberian Pipit). Our results also suggest that the Water Pipit A. spinoletta deserves taxonomic reassessment as its lineages are highly divergent in acoustics and mtDNA, while mtDNA relationships suggest paraphyly relative to the Rock Pipit A. petrosus. Our work highlights the crucial importance of integrative approaches in taxonomy and the usefulness of bioacoustics in studying cryptic diversity.

RevDate: 2024-01-16
CmpDate: 2024-01-16

Hoare RJB, Patrick BH, Buckley TR, et al (2023)

Wing pattern variation and DNA barcodes defy taxonomic splitting in the New Zealand Pimelea Looper Notoreas perornata (Walker) (Lepidoptera: Geometridae: Larentiinae): the importance of populations as conservation units.

Zootaxa, 5346(1):1-27.

The endemic Notoreas perornata (Walker, 1863) complex (Lepidoptera: Geometridae: Larentiinae) from the North Island and northern South Island of New Zealand is reviewed. Larvae feed on Pimelea spp. (Thymelaeaceae), frequently in highly fragmented and threatened shrubland habitats. Allopatric populations tend to differ in size and wing pattern characteristics, but not in genitalia; moreover extensive variation renders recognition of subspecies / allopatric species based on any species concept problematic. A mitochondrial DNA gene tree is not congruent with morphology and indicates rapid recent divergence that has not settled into diagnosable lineages. Based on our results, we synonymise Notoreas simplex Hudson, 1898 with N. perornata (Walker, 1863), and retain N. perornata as a single, highly diverse but monotypic species. All known populations are illustrated to display variation. For conservation purposes, we recommend the continued recognition within the species of 10 populations or groups of populations that appear to be on the way to diverging at subspecific level based on morphological and/or DNA data. The conservation status of all these populations is reviewed. One conservation unit, comprising the populations from Westland, has not been seen since 1998 and is feared possibly extinct.

RevDate: 2024-01-16
CmpDate: 2024-01-16

Antoniolli HRM, Carvalho TL, Gottschalk MS, et al (2024)

Systematics and spatio-temporal evolutionary patterns of the flavopilosa group of Drosophila (Diptera, Drosophilidae).

Zootaxa, 5399(1):1-18.

The Drosophila flavopilosa group comprises morphologically cryptic species that are ecologically restricted to feeding, breeding and ovipositing on flowers of Cestrum and Sessea (Solanaceae). Previous studies confirmed the monophyly of the group and the success of DNA barcoding in identifying a subset of its species, but several others remain yet to be evaluated. Furthemore, the taxonomy of the group remains incomplete, with only nine of the 17 species assigned to subgroups. Here, we accessed the phylogenetic relationships and spatio-temporal evolutionary patterns of the flavopilosa group based on a mitochondrial and two nuclear genes, providing the first molecular support to the subdivision of the group and suggesting a new taxonomic scheme for its species. Barcoding proved to be an effective tool, as all species were reciprocally monophyletic and different analyses of species delimitation yielded congruent results. The close relationship of D. flavopilosa with D. cestri and D. cordeiroi was strongly supported, suggesting that the latter should be placed in the flavopilosa subgroup together with the first. Furthermore, D. mariaehelenae was positioned as sister to D. incompta, supporting its inclusion in the nesiota subgroup. Despite new taxonomic assignments, the synapomorphic status of the diagnostic characters proposed for both subgroups was supported. Based on them, each of the remaining species were placed into one of both subgroups. Divergence time estimates suggest that their diversification coincided with the divergence of Sessea and Cestrum, providing an interesting case of coevolution.

RevDate: 2024-01-15
CmpDate: 2024-01-15

Cao L, Chen P, Hou X, et al (2024)

rDNA and mtDNA analysis for the identification of genetic characters in the hybrid grouper derived from hybridization of Cromileptes altivelis (female) × Epinephelus lanceolatus (male).

BMC genomic data, 25(1):5.

BACKGROUND: Hybridization is a useful strategy to produce offspring with more desirable phenotypic characteristics than those of parents. The hybrid grouper derived from the cross of Cromileptes altivelis (♀, 2n = 48) with Epinephelus lanceolatus (♂, 2n = 48) exhibits improved growth compared with its female parent, which makes it valuable to aquaculture. However, the genetic traits of the hybrid grouper are poorly understood.

RESULTS: The observations showed that the hybrid grouper was diploid (2n = 48) and displayed intermediate morphology with the parent's measurable characteristics. The ribosomal DNA (rDNA) and mitochondria DNA (mtDNA) were characterized at molecular and phylogenetic level. High similarity and low genetic distance of 5S rDNA and mtDNA sequences between the hybrid grouper and C. altivelis showed that the hybrid grouper had a closer genetic relationship with female parents. The reconstructed phylogenetic tree based on COI gene and D-loop region of mtDNA recovered that mtDNA was maternally inherited in the hybrid grouper. Additionally, the DNA methylation level of 5S rDNA intergenic spacers (IGS) sequence was tested in here. The results showed that the DNA methylation status of the hybrid grouper was significantly lower than that of C. altivelis.

CONCLUSION: Results of this study provide important data on the genetic characteristics of the hybrid derived from the cross of C. altivelis and E. lanceolatus, and contribute the knowledge of both evolution and marine fish breeding.

RevDate: 2024-01-12
CmpDate: 2024-01-12

Crino OL, Head ML, Jennions MD, et al (2024)

Mitochondrial function and sexual selection: can physiology resolve the 'lek paradox'?.

The Journal of experimental biology, 227(2):.

Across many taxa, males use elaborate ornaments or complex displays to attract potential mates. Such sexually selected traits are thought to signal important aspects of male 'quality'. Female mating preferences based on sexual traits are thought to have evolved because choosy females gain direct benefits that enhance their lifetime reproductive success (e.g. greater access to food) and/or indirect benefits because high-quality males contribute genes that increase offspring fitness. However, it is difficult to explain the persistence of female preferences when males only provide genetic benefits, because female preferences should erode the heritable genetic variation in fitness that sexually selected traits signal. This 'paradox of the lek' has puzzled evolutionary biologists for decades, and inspired many hypotheses to explain how heritable variation in sexually selected traits is maintained. Here, we discuss how factors that affect mitochondrial function can maintain variation in sexually selected traits despite strong female preferences. We discuss how mitochondrial function can influence the expression of sexually selected traits, and we describe empirical studies that link the expression of sexually selected traits to mitochondrial function. We explain how mothers can affect mitochondrial function in their offspring by (a) influencing their developmental environment through maternal effects and (b) choosing a mate to increase the compatibility of mitochondrial and nuclear genes (i.e. the 'mitonuclear compatibility model of sexual selection'). Finally, we discuss how incorporating mitochondrial function into models of sexual selection might help to resolve the paradox of the lek, and we suggest avenues for future research.

RevDate: 2024-01-13
CmpDate: 2024-01-12

Baleva MV, Piunova U, Chicherin I, et al (2023)

Mitochondrial Protein SLIRP Affects Biosynthesis of Cytochrome c Oxidase Subunits in HEK293T Cells.

International journal of molecular sciences, 25(1):.

Mitochondria carry out various vital roles in eukaryotic cells, including ATP energy synthesis, the regulation of apoptosis, Fe-S cluster formation, and the metabolism of fatty acids, amino acids, and nucleotides. Throughout evolution, mitochondria lost most of their ancestor's genome but kept the replication, transcription, and translation machinery. Protein biosynthesis in mitochondria is specialized in the production of highly hydrophobic proteins encoded by mitochondria. These proteins are components of oxidative phosphorylation chain complexes. The coordination of protein synthesis must be precise to ensure the correct assembly of nuclear-encoded subunits for these complexes. However, the regulatory mechanisms of mitochondrial translation in human cells are not yet fully understood. In this study, we examined the contribution of the SLIRP protein in regulating protein biosynthesis in mitochondria. Using a click-chemistry approach, we discovered that deletion of the SLIRP gene disturbs mitochondrial translation, leading to the dysfunction of complexes I and IV, but it has no significant effect on complexes III and V. We have shown that this protein interacts only with the small subunit of the mitochondrial ribosome, which may indicate its involvement in the regulation of the mitochondrial translation initiation stage.

RevDate: 2024-01-13
CmpDate: 2024-01-12

Korolija M, Sukser V, K Vlahoviček (2024)

Mitochondrial point heteroplasmy: insights from deep-sequencing of human replicate samples.

BMC genomics, 25(1):48.

BACKGROUND: Human mitochondrial heteroplasmy is an extensively investigated phenomenon in the context of medical diagnostics, forensic identification and molecular evolution. However, technical limitations of high-throughput sequencing hinder reliable determination of point heteroplasmies (PHPs) with minor allele frequencies (MAFs) within the noise threshold.

RESULTS: To investigate the PHP landscape at an MAF threshold down to 0.1%, we sequenced whole mitochondrial genomes at approximately 7.700x coverage, in multiple technical and biological replicates of longitudinal blood and buccal swab samples from 11 human donors (159 libraries in total). The results obtained by two independent sequencing platforms and bioinformatics pipelines indicate distinctive PHP patterns below and above the 1% MAF cut-off. We found a high inter-individual prevalence of low-level PHPs (MAF < 1%) at polymorphic positions of the mitochondrial DNA control region (CR), their tissue preference, and a tissue-specific minor allele linkage. We also established the position-dependent potential of minor allele expansion in PHPs, and short-term PHP instability in a mitotically active tissue. We demonstrate that the increase in sensitivity of PHP detection to minor allele frequencies below 1% within a robust experimental and analytical pipeline, provides new information with potential applicative value.

CONCLUSIONS: Our findings reliably show different mutational loads between tissues at sub-1% allele frequencies, which may serve as an informative medical biomarker of time-dependent, tissue-specific mutational burden, or help discriminate forensically relevant tissues in a single person, close maternal relatives or unrelated individuals of similar phylogenetic background.

RevDate: 2024-01-12
CmpDate: 2024-01-12

Liu J, Hu JY, DZ Li (2024)

Remarkable mitochondrial genome heterogeneity in Meniocus linifolius (Brassicaceae).

Plant cell reports, 43(2):36.

Detailed analyses of 16 genomes identified a remarkable acceleration of mutation rate, hence mitochondrial sequence and structural heterogeneity, in Meniocus linifolius (Brassicaceae). The powerhouse, mitochondria, in plants feature high levels of structural variation, while the encoded genes are normally conserved. However, the substitution rates and spectra of mitochondria DNA within the Brassicaceae, a family with substantial scientific and economic importance, have not been adequately deciphered. Here, by analyzing three newly assembled and 13 known mitochondrial genomes (mitogenomes), we report the highly variable genome structure and mutation rates in Brassicaceae. The genome sizes and GC contents are 196,604 bp and 46.83%, 288,122 bp and 44.79%, and 287,054 bp and 44.93%, for Meniocus linifolius (Mli), Crucihimalaya lasiocarpa (Cla), and Lepidium sativum (Lsa), respectively. In total, 29, 33, and 34 protein-coding genes (PCGs) and 14, 18, and 18 tRNAs are annotated for Mli, Cla, and Lsa, respectively, while all mitogenomes contain one complete circular molecule with three rRNAs and abundant RNA editing sites. The Mli mitogenome features four conformations likely mediated by the two pairs of long repeats, while at the same time seems to have an unusual evolutionary history due to higher GC content, loss of more genes and sequences, but having more repeats and plastid DNA insertions. Corroborating with these, an ambiguous phylogenetic position with long branch length and elevated synonymous substitution rate in nearly all PCGs are observed for Mli. Taken together, our results reveal a high level of mitogenome heterogeneity at the family level and provide valuable resources for further understanding the evolutionary pattern of organelle genomes in Brassicaceae.

RevDate: 2024-01-08

Huttner WB, Heide M, Mora-Bermúdez F, et al (2024)

Neocortical neurogenesis in development and evolution-Human-specific features.

The Journal of comparative neurology [Epub ahead of print].

In this review, we focus on human-specific features of neocortical neurogenesis in development and evolution. Two distinct topics will be addressed. In the first section, we discuss the expansion of the neocortex during human evolution and concentrate on the human-specific gene ARHGAP11B. We review the ability of ARHGAP11B to amplify basal progenitors and to expand a primate neocortex. We discuss the contribution of ARHGAP11B to neocortex expansion during human evolution and its potential implications for neurodevelopmental disorders and brain tumors. We then review the action of ARHGAP11B in mitochondria as a regulator of basal progenitor metabolism, and how it promotes glutaminolysis and basal progenitor proliferation. Finally, we discuss the increase in cognitive performance due to the ARHGAP11B-induced neocortical expansion. In the second section, we focus on neocortical development in modern humans versus Neanderthals. Specifically, we discuss two recent findings pointing to differences in neocortical neurogenesis between these two hominins that are due to a small number of amino acid substitutions in certain key proteins. One set of such proteins are the kinetochore-associated proteins KIF18a and KNL1, where three modern human-specific amino acid substitutions underlie the prolongation of metaphase during apical progenitor mitosis. This prolongation in turn is associated with an increased fidelity of chromosome segregation to the apical progenitor progeny during modern human neocortical development, with implications for the proper formation of radial units. Another such key protein is transketolase-like 1 (TKTL1), where a single modern human-specific amino acid substitution endows TKTL1 with the ability to amplify basal radial glia, resulting in an increase in upper-layer neuron generation. TKTL1's ability is based on its action in the pentose phosphate pathway, resulting in increased fatty acid synthesis. The data imply greater neurogenesis during neocortical development in modern humans than Neanderthals due to TKTL1, in particular in the developing frontal lobe.

RevDate: 2024-01-09

Riew TR, Hwang JW, Jin X, et al (2023)

Astrocytes are involved in the formation of corpora amylacea-like structures from neuronal debris in the CA1 region of the rat hippocampus after ischemia.

Frontiers in cellular neuroscience, 17:1308247.

Recently, we demonstrated that the corpora amylacea (CA), a glycoprotein-rich aggregate frequently found in aged brains, accumulates in the ischemic hippocampus and that osteopontin (OPN) mediates the entire process of CA formation. Therefore, this study aimed to elucidate the mechanisms by which astrocytes and microglia participate in CA formation during the late phase (4-12 weeks) of brain ischemia. Based on various morphological analyses, including immunohistochemistry, in situ hybridization, immunoelectron microscopy, and correlative light and electron microscopy, we propose that astrocytes are the primary cells responsible for CA formation after ischemia. During the subacute phase after ischemia, astrocytes, rather than microglia, express Opn messenger ribonucleic acid and OPN protein, a surrogate marker and key component of CA. Furthermore, the specific localization of OPN in the Golgi complex suggests that it is synthesized and secreted by astrocytes. Astrocytes were in close proximity to type I OPN deposits, which accumulated in the mitochondria of degenerating neurons before fully forming the CA (type III OPN deposits). Throughout CA formation, astrocytes remained closely attached to OPN deposits, with their processes exhibiting well-developed gap junctions. Astrocytic cytoplasmic protein S100β, a calcium-binding protein, was detected within the fully formed CA. Additionally, ultrastructural analysis revealed direct contact between astroglial fibrils and the forming facets of the CA. Overall, we demonstrated that astrocytes play a central role in mediating CA formation from the initial stages of OPN deposit accumulation to the evolution of fully formed CA following transient ischemia in the hippocampus.

RevDate: 2024-01-08

Sizek H, Deritei D, Fleig K, et al (2023)

Unlocking Mitochondrial Dysfunction-Associated Senescence (MiDAS) with NAD [+] - a Boolean Model of Mitochondrial Dynamics and Cell Cycle Control.

bioRxiv : the preprint server for biology pii:2023.12.18.572194.

UNLABELLED: The steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. The secretome of senescent cells promotes chronic inflammation, contains growth and transforming signals, and causes chronic oxidative stress. The latter is primarily due to dysfunctional mitochondria often seen in senescent cells. Aging cell states are highly heterogeneous. 'Deep senescent' cells rely on healthy mitochondria to fuel a strong proinflammatory secretome. In parallel, the triggers of deep senescence also generate cells with mitochondrial dysfunction, and sufficient energy deficit to alter their secretome - a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here we offer a mechanistic explanation for the molecular processes leading to MiDAS. To do this we have built a Boolean regulatory network model able to reproduce mitochondrial dynamics during cell cycle progression (hyper-fusion at the G1/S boundary, fission in mitosis), apoptosis (fission and dysfunction) and glucose starvation (reversible hyper-fusion), as well as MiDAS in response to SIRT3 knockdown or oxidative stress. Our model also recapitulates the protective role of NAD [+] and external pyruvate. We offer testable predictions about the growth factor- and glucose-dependence of MiDAS and its reversibility at different stages of reactive oxygen species (ROS)-induced senescence. Our model opens the door to modeling distinct stages of DNA-damage induced senescence, the relationship between senescence and epithelial-to-mesenchymal transition in cancer and building multiscale models of tissue aging.

HIGHLIGHTS: Boolean regulatory network model reproduces mitochondrial dynamics during cell cycle progression, apoptosis, and glucose starvation. Model offers a mechanistic explanation for the positive feedback loop that locks in Mitochondrial Dysfunction-Associated Senescence (MiDAS), involving autophagy-resistant hyperfused but dysfunctional mitochondria. Model reproduces ROS-mediated mitochondrial dysfunction and suggests that MiDAS is part of the early phase of damage-induced senescence. Model predicts that cancer-driving mutations that bypass the G1/S checkpoint generally increase the incidence of MiDAS, with the notable exception of p53 loss.

RevDate: 2024-01-10
CmpDate: 2024-01-09

Prokkola JM, Chew KK, Anttila K, et al (2024)

Tissue-specific metabolic enzyme levels covary with whole-animal metabolic rates and life-history loci via epistatic effects.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 379(1896):20220482.

Metabolic rates, including standard (SMR) and maximum (MMR) metabolic rate have often been linked with life-history strategies. Variation in context- and tissue-level metabolism underlying SMR and MMR may thus provide a physiological basis for life-history variation. This raises a hypothesis that tissue-specific metabolism covaries with whole-animal metabolic rates and is genetically linked to life history. In Atlantic salmon (Salmo salar), variation in two loci, vgll3 and six6, affects life history via age-at-maturity as well as MMR. Here, using individuals with known SMR and MMR with different vgll3 and six6 genotype combinations, we measured proxies of mitochondrial density and anaerobic metabolism, i.e. maximal activities of the mitochondrial citrate synthase (CS) and lactate dehydrogenase (LDH) enzymes, in four tissues (heart, intestine, liver, white muscle) across low- and high-food regimes. We found enzymatic activities were related to metabolic rates, mainly SMR, in the intestine and heart. Individual loci were not associated with the enzymatic activities, but we found epistatic effects and genotype-by-environment interactions in CS activity in the heart and epistasis in LDH activity in the intestine. These effects suggest that mitochondrial density and anaerobic capacity in the heart and intestine may partly mediate variation in metabolic rates and life history via age-at-maturity. This article is part of the theme issue 'The evolutionary significance of variation in metabolic rates'.

RevDate: 2024-01-10
CmpDate: 2024-01-09

Thoral E, Dargère L, Medina-Suárez I, et al (2024)

Non-lethal sampling for assessment of mitochondrial function does not affect metabolic rate and swimming performance.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 379(1896):20220483.

A fundamental issue in the metabolic field is whether it is possible to understand underlying mechanisms that characterize individual variation. Whole-animal performance relies on mitochondrial function as it produces energy for cellular processes. However, our lack of longitudinal measures to evaluate how mitochondrial function can change within and among individuals and with environmental context makes it difficult to assess individual variation in mitochondrial traits. The aims of this study were to test the repeatability of muscle mitochondrial metabolism by performing two biopsies of red muscle, and to evaluate the effects of biopsies on whole-animal performance in goldfish Carassius auratus. Our results show that basal mitochondrial respiration and net phosphorylation efficiency are repeatable at 14-day intervals. We also show that swimming performance (optimal cost of transport and critical swimming speed) was repeatable in biopsied fish, whereas the repeatability of individual oxygen consumption (standard and maximal metabolic rates) seemed unstable over time. However, we noted that the means of individual and mitochondrial traits did not change over time in biopsied fish. This study shows that muscle biopsies allow the measurement of mitochondrial metabolism without sacrificing animals and that two muscle biopsies 14 days apart affect the intraspecific variation in fish performance without affecting average performance of individuals. This article is part of the theme issue 'The evolutionary significance of variation in metabolic rates'.

RevDate: 2024-01-07

Zhang D, Jakovlić I, Zou H, et al (2024)

Strong mitonuclear discordance in the phylogeny of Neodermata and evolutionary rates of Polyopisthocotylea.

International journal for parasitology pii:S0020-7519(24)00001-8 [Epub ahead of print].

The genomic evolution of Polyopisthocotylea remains poorly understood in comparison to the remaining three classes of Neodermata: Monopisthocotylea, Cestoda, and Trematoda. Moreover, the evolutionary sequence of major events in the phylogeny of Neodermata remains unresolved. Herein we sequenced the mitogenome and transcriptome of the polyopisthocotylean Diplorchis sp., and conducted comparative evolutionary analyses using nuclear (nDNA) and mitochondrial (mtDNA) genomic datasets of Neodermata. We found strong mitonuclear discordance in the phylogeny of Neodermata. Polyopisthocotylea exhibited striking mitonuclear discordance in relative evolutionary rates: the fastest-evolving mtDNA in Neodermata and a comparatively slowly-evolving nDNA genome. This was largely attributable to its very long stem branch in mtDNA topologies, not exhibited by the nDNA data. We found indications that the fast evolution of mitochondrial genomes of Polyopisthocotylea may be driven both by relaxed purifying selection pressures and elevated levels of directional selection. We identified mitochondria-associated genes encoded in the nuclear genome: they exhibited unique evolutionary rates, but not correlated with the evolutionary rate of mtDNA, and there is no evidence for compensatory evolution (they evolved slower than the rest of the genome). Finally, there appears to exist an exceptionally large (≈6.3 kb) nuclear mitochondrial DNA segment (numt) in the nuclear genome of newly sequenced Diplorchis sp. A 3'-end segment of the 16S rRNA gene encoded by the numt was expressed, suggesting that this gene acquired novel, regulatory functions after the transposition to the nuclear genome. In conclusion, Polyopisthocotylea appears to be the lineage with the fastest-evolving mtDNA sequences among all of Bilateria, but most of the substitutions were accumulated deep in the evolutionary history of this lineage. As the nuclear genome does not exhibit a similar pattern, the circumstances underpinning this evolutionary phenomenon remain a mystery.

RevDate: 2024-01-08
CmpDate: 2024-01-08

Yonezawa T, Mannen H, Honma K, et al (2024)

Origin and spatial population structure of Malagasy native chickens based on mitochondrial DNA.

Scientific reports, 14(1):569.

Since Malagasy human culture became established in a multi-layered way by genetic admixture of Austronesian (Indonesia), Bantu (East Africa) and West Asian populations, the Malagasy native livestock should also have originated from these regions. While recent genetic studies revealed that Malagasy native dogs and goats were propagated from Africa, the origin of Malagasy native chickens is still controversial. Here, we conducted a phylogeographic analysis of the native chickens, focusing on the historical relationships among the Indian Ocean rim countries and based on mitochondrial D-loop sequences. Although previous work suggested that the rare Haplogroup D occurs with high frequencies in Island Southeast Asia-Pacific, East Africa and Madagascar, the major mitochondrial lineage in Malagasy populations is actually not Haplogroup D but the Sub-haplogroup C2, which is also observed in East Africa, North Africa, India and West Asia. We demonstrate that the Malagasy native chickens were propagated directly from West Asia (including India and North Africa), and not via East Africa. Furthermore, they display clear genetic differentiation within Madagascar, separated into the Highland and Lowland regions as seen in the human genomic landscape on this island. Our findings provide new insights for better understanding the intercommunion of material/non-material cultures within and around Madagascar.

RevDate: 2024-01-04

Chi HM, Davies MR, Garcia SM, et al (2024)

Defining Endogenous Mitochondrial Transfer in Muscle After Rotator Cuff Injury.

The American journal of sports medicine [Epub ahead of print].

BACKGROUND: Rotator cuff muscle degeneration leads to poor clinical outcomes for patients with rotator cuff tears. Fibroadipogenic progenitors (FAPs) are resident muscle stem cells with the ability to differentiate into fibroblasts as well as white and beige adipose tissue. Induction of the beige adipose phenotype in FAPs has been shown to improve muscle quality after rotator cuff tears, but the mechanisms of how FAPs exert their beneficial effects have not been fully elucidated.

PURPOSE: To study the horizontal transfer of mitochondria from FAPs to myogenic cells and examine the effects of β-agonism on this novel process.

STUDY DESIGN: Controlled laboratory study.

METHODS: In mice that had undergone a massive rotator cuff tear, single-cell RNA sequencing was performed on isolated FAPs for genes associated with mitochondrial biogenesis and transfer. Murine FAPs were isolated by fluorescence-activated cell sorting and treated with a β-agonist versus control. FAPs were stained with mitochondrial dyes and cocultured with recipient C2C12 myoblasts, and the rate of transfer was measured after 24 hours by flow cytometry. PdgfraCre[ERT]/MitoTag mice were generated to study the effects of a rotator cuff injury on mitochondrial transfer. PdgfraCre[ERT]/tdTomato mice were likewise generated to perform lineage tracing of PDGFRA[+] cells in this injury model. Both populations of transgenic mice underwent tendon transection and denervation surgery, and MitoTag-labeled mitochondria from Pdgfra[+] FAPs were visualized by fluorescent microscopy, spinning disk confocal microscopy, and 2-photon microscopy; overall mitochondrial quantity was compared between mice treated with β-agonists and dimethyl sulfoxide.

RESULTS: Single-cell RNA sequencing in mice that underwent rotator cuff tear demonstrated an association between transcriptional markers of adipogenic differentiation and genes associated with mitochondrial biogenesis. In vitro cocultures of murine FAPs with C2C12 cells revealed that treatment of cells with a β-agonist increased mitochondrial transfer compared to control conditions (17.8% ± 9.9% to 99.6% ± 0.13% P < .0001). Rotator cuff injury in PdgfraCre[ERT]/MitoTag mice resulted in a robust increase in MitoTag signal in adjacent myofibers compared with uninjured mice. No accumulation of tdTomato signal from PDGFRA[+] cells was seen in injured fibers at 6 weeks after injury, suggesting that FAPs do not fuse with injured muscle fibers but rather contribute their mitochondria.

CONCLUSION: The authors have described a novel process of endogenous mitochondrial transfer that can occur within the injured rotator cuff between FAPs and myogenic cells. This process may be leveraged therapeutically with β-agonist treatment and represents an exciting target for improving translational therapies available for rotator cuff muscle degeneration.

CLINICAL RELEVANCE: Promoting endogenous mitochondrial transfer may represent a novel translational strategy to address muscle degeneration after rotator cuff tears.

RevDate: 2024-01-14
CmpDate: 2024-01-05

Cui M, Yamano K, Yamamoto K, et al (2024)

HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence.

Proceedings of the National Academy of Sciences of the United States of America, 121(2):e2306454120.

Mitochondrial and lysosomal functions are intimately linked and are critical for cellular homeostasis, as evidenced by the fact that cellular senescence, aging, and multiple prominent diseases are associated with concomitant dysfunction of both organelles. However, it is not well understood how the two important organelles are regulated. Transcription factor EB (TFEB) is the master regulator of lysosomal function and is also implicated in regulating mitochondrial function; however, the mechanism underlying the maintenance of both organelles remains to be fully elucidated. Here, by comprehensive transcriptome analysis and subsequent chromatin immunoprecipitation-qPCR, we identified hexokinase domain containing 1 (HKDC1), which is known to function in the glycolysis pathway as a direct TFEB target. Moreover, HKDC1 was upregulated in both mitochondrial and lysosomal stress in a TFEB-dependent manner, and its function was critical for the maintenance of both organelles under stress conditions. Mechanistically, the TFEB-HKDC1 axis was essential for PINK1 (PTEN-induced kinase 1)/Parkin-dependent mitophagy via its initial step, PINK1 stabilization. In addition, the functions of HKDC1 and voltage-dependent anion channels, with which HKDC1 interacts, were essential for the clearance of damaged lysosomes and maintaining mitochondria-lysosome contact. Interestingly, HKDC1 regulated mitophagy and lysosomal repair independently of its prospective function in glycolysis. Furthermore, loss function of HKDC1 accelerated DNA damage-induced cellular senescence with the accumulation of hyperfused mitochondria and damaged lysosomes. Our results show that HKDC1, a factor downstream of TFEB, maintains both mitochondrial and lysosomal homeostasis, which is critical to prevent cellular senescence.

RevDate: 2024-01-06
CmpDate: 2024-01-05

Graham AM, Lavretsky P, Wilson RE, et al (2024)

High-altitude adaptation is accompanied by strong signatures of purifying selection in the mitochondrial genomes of three Andean waterfowl.

PloS one, 19(1):e0294842.

Evidence from a variety of organisms points to convergent evolution on the mitochondria associated with a physiological response to oxygen deprivation or temperature stress, including mechanisms for high-altitude adaptation. Here, we examine whether demography and/or selection explains standing mitogenome nucleotide diversity in high-altitude adapted populations of three Andean waterfowl species: yellow-billed pintail (Anas georgica), speckled teal (Anas flavirostris), and cinnamon teal (Spatula cyanoptera). We compared a total of 60 mitogenomes from each of these three duck species (n = 20 per species) across low and high altitudes and tested whether part(s) or all of the mitogenome exhibited expected signatures of purifying selection within the high-altitude populations of these species. Historical effective population sizes (Ne) were inferred to be similar between high- and low-altitude populations of each species, suggesting that selection rather than genetic drift best explains the reduced genetic variation found in mitochondrial genes of high-altitude populations compared to low-altitude populations of the same species. Specifically, we provide evidence that establishment of these three Andean waterfowl species in the high-altitude environment, coincided at least in part with a persistent pattern of negative purifying selection acting on oxidative phosphorylation (OXPHOS) function of the mitochondria. Our results further reveal that the extent of gene-specific purifying selection has been greatest in the speckled teal, the species with the longest history of high-altitude occupancy.

RevDate: 2024-01-03

Labbadia J (2023)

Potential roles for mitochondria-to-HSF1 signaling in health and disease.

Frontiers in molecular biosciences, 10:1332658.

The ability to respond rapidly and efficiently to protein misfolding is crucial for development, reproduction and long-term health. Cells respond to imbalances in cytosolic/nuclear protein homeostasis through the Heat Shock Response, a tightly regulated transcriptional program that enhances protein homeostasis capacity by increasing levels of protein quality control factors. The Heat Shock Response is driven by Heat Shock Factor 1, which is rapidly activated by the appearance of misfolded proteins and drives the expression of genes encoding molecular chaperones and protein degradation factors, thereby restoring proteome integrity. HSF1 is critical for organismal health, and this has largely been attributed to the preservation of cytosolic and nuclear protein homeostasis. However, evidence is now emerging that HSF1 is also a key mediator of mitochondrial function, raising the possibility that many of the health benefits conferred by HSF1 may be due to the maintenance of mitochondrial homeostasis. In this review, I will discuss our current understanding of the interplay between HSF1 and mitochondria and consider how mitochondria-to-HSF1 signaling may influence health and disease susceptibility.

RevDate: 2024-01-03

Hambardikar V, Akosah YA, Scoma ER, et al (2023)

Toolkit for cellular studies of mammalian mitochondrial inorganic polyphosphate.

Frontiers in cell and developmental biology, 11:1302585.

Introduction: Inorganic polyphosphate (polyP) is an ancient polymer which is extremely well-conserved throughout evolution, and found in every studied organism. PolyP is composed of orthophosphates linked together by high-energy bonds, similar to those found in ATP. The metabolism and the functions of polyP in prokaryotes and simple eukaryotes are well understood. However, little is known about its physiological roles in mammalian cells, mostly due to its unknown metabolism and lack of systematic methods and effective models for the study of polyP in these organisms. Methods: Here, we present a comprehensive set of genetically modified cellular models to study mammalian polyP. Specifically, we focus our studies on mitochondrial polyP, as previous studies have shown the potent regulatory role of mammalian polyP in the organelle, including bioenergetics, via mechanisms that are not yet fully understood. Results: Using SH-SY5Y cells, our results show that the enzymatic depletion of mitochondrial polyP affects the expression of genes involved in the maintenance of mitochondrial physiology, as well as the structure of the organelle. Furthermore, this depletion has deleterious effects on mitochondrial respiration, an effect that is dependent on the length of polyP. Our results also show that the depletion of mammalian polyP in other subcellular locations induces significant changes in gene expression and bioenergetics; as well as that SH-SY5Y cells are not viable when the amount and/or the length of polyP are increased in mitochondria. Discussion: Our findings expand on the crucial role of polyP in mammalian mitochondrial physiology and place our cell lines as a valid model to increase our knowledge of both mammalian polyP and mitochondrial physiology.

RevDate: 2024-01-08
CmpDate: 2024-01-03

Yang X, Li G, Lou P, et al (2024)

Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.

Proceedings of the National Academy of Sciences of the United States of America, 121(1):e2307395120.

Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD[+] depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD[+] levels with NAD[+] or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention.

RevDate: 2024-01-06
CmpDate: 2024-01-03

Kuprina K, Smorkatcheva A, Rudyk A, et al (2023)

Numerous insertions of mitochondrial DNA in the genome of the northern mole vole, Ellobius talpinus.

Molecular biology reports, 51(1):36.

BACKGROUND: Ellobius talpinus is a subterranean rodent representing an attractive model in population ecology studies due to its highly special lifestyle and sociality. In such studies, mitochondrial DNA (mtDNA) is widely used. However, if nuclear copies of mtDNA, aka NUMTs, are present, they may co-amplify with the target mtDNA fragment, generating misleading results. The aim of this study was to determine whether NUMTs are present in E. talpinus.

METHODS AND RESULTS: PCR amplification of the putative mtDNA CytB-D-loop fragment using 'universal' primers from 56 E. talpinus samples produced multiple double peaks in 90% of the sequencing chromatograms. To reveal NUMTs, molecular cloning and sequencing of PCR products of three specimens was conducted, followed by phylogenetic analysis. The pseudogene nature of three out of the seven detected haplotypes was confirmed by their basal positions in relation to other Ellobius haplotypes in the phylogenetic tree. Additionally, 'haplotype B' was basal in relation to other E. talpinus haplotypes and found present in very distant sampling sites. BLASTN search revealed 195 NUMTs in the E. talpinus nuclear genome, including fragments of all four PCR amplified pseudogenes. Although the majority of the NUMTs studied were short, the entire mtDNA had copies in the nuclear genome. The most numerous NUMTs were found for rrnL, COXI, and D-loop.

CONCLUSIONS: Numerous NUMTs are present in E. talpinus and can be difficult to discriminate against mtDNA sequences. Thus, in future population or phylogenetic studies in E. talpinus, the possibility of cryptic NUMTs amplification should always be taken into account.

RevDate: 2024-01-06
CmpDate: 2023-12-28

Shen Q, Yuan Y, J Jin (2023)

[Relationship between Notch signaling pathway and mitochondrial energy metabolism].

Zhonghua wei zhong bing ji jiu yi xue, 35(12):1321-1326.

Notch signaling pathway is a highly conserved signaling pathway in the process of evolution. It is composed of three parts: Notch receptor, ligand and effector molecules responsible for intracellular signal transduction. It plays an important role in cell proliferation, differentiation, development, migration, apoptosis and other processes, and has a regulatory effect on tissue homeostasis and homeostasis. Mitochondria are the sites of oxidative metabolism in eukaryotes, where sugars, fats and proteins are finally oxidized to release energy. In recent years, the regulation of Notch signaling pathway on mitochondrial energy metabolism has attracted more and more attention. A large number of data have shown that Notch signaling pathway has a significant effect on mitochondrial energy metabolism, but the relationship between Notch signaling pathway and mitochondrial energy metabolism needs to be specifically and systematically discussed. In this paper, the relationship between Notch signaling pathway and mitochondrial energy metabolism is reviewed, in order to improve the understanding of them and provide new ideas for the treatment of related diseases.

RevDate: 2023-12-28
CmpDate: 2023-12-28

Yang J, Gao J, Li W, et al (2023)

[Identification and expression analysis of apple PDHB-1 gene family].

Sheng wu gong cheng xue bao = Chinese journal of biotechnology, 39(12):4965-4981.

Pyruvate dehydrogenase E1 component subunit beta-1 (PDHB-1) is a gene encoding the β-subunit of pyruvate dehydrogenase complex, which plays an important role in fruit acid accumulation. The aim of this study was to investigate the evolution characteristics of apple PDHB-1 family and its expression in apples with different acid contents. Bioinformatics analysis was performed using databases including NCBI, Pfam and software including ClustalX, MEGA, and TBtools. By combining titratable acid content determination and quantitative real-time PCR (qRT-PCR), the expression of this family genes in the peel and pulp of apple 'Asda' and 'Chengji No.1' with different acid content were obtained, respectively. The family members were mainly located in chloroplast, cytoplasm and mitochondria. α-helix and random coil were the main factors for the formation of secondary structure in this family. Tissue-specific expression profiles showed that the expression of most members were higher in fruit than in other tissues. qRT-PCR results showed that the expression profile of most members was consistent with the profile of titratable acid contents. In the peel, the expression levels of 14 members in 'Asda' apples with high acid content were significantly higher than that in 'Chengji No.1' apples with low acid content, where the expression difference of MdPDHB1-15 was the most significant. In the pulp, the expression levels of 17 members in 'Asda' apples were significantly higher than that in 'Chengji No.1' apples, where MdPDHB1-01 was the most highly expressed. It was predicted that PDHB-1 gene family in apple plays an important role in the regulation of fruit acidity.

RevDate: 2023-12-30

Buonvicino D, Pratesi S, Ranieri G, et al (2023)

The mitochondriogenic but not the immunosuppressant effects of mTOR inhibitors prompt neuroprotection and delay disease evolution in a mouse model of progressive multiple sclerosis.

Neurobiology of disease, 191:106387 pii:S0969-9961(23)00403-5 [Epub ahead of print].

INTRODUCTION: Purportedly, the progression of multiple sclerosis (MS) occurs when neurodegenerative processes due to derangement of axonal bioenergetics take over the autoimmune response. However, a clear picture of the causative interrelationship between autoimmunity and axonal mitochondrial dysfunction in progressive MS (PMS) pathogenesis waits to be provided.

METHODS: In the present study, by adopting the NOD mouse model of PMS, we compared the pharmacological effects of the immunosuppressants dexamethasone and fingolimod with those of mTOR inhibitors rapamycin and everolimus that, in addition to immunosuppression, also regulate mitochondrial functioning. Female Non-Obese Diabetic (NOD) mice were immunized with MOG35-55 and treated with drugs to evaluate functional, immune and mitochondrial parameters during disease evolution.

RESULTS: We found that dexamethasone and fingolimod did not affect the pattern of progression as well as survival. Conversely, mTOR inhibitors rapamycin and everolimus delayed disease progression and robustly extended survival of immunized mice. The same effects were obtained when treatment was delayed by 30 days after immunization. Remarkably, dexamethasone and fingolimod prompted the same degree of immunosuppression of rapamycin within both spleen and spinal cord of mice. However, only rapamycin prompted mitochondriogenesis by increasing mitochondrial content, and expression of several mitochondrial respiratory complex subunits, thereby preventing mtDNA reduction in the spinal cords of immunized mice. These pharmacodynamic effects were not reproduced in healthy NOD mice, suggesting a disease context-dependent pharmacodynamic effect.

DISCUSSION: Data corroborate the key role of mitochondriogenesis to treatment of MS progression, and for the first time disclose the translational potential of mTOR inhibitors in PMS therapy.

RevDate: 2024-01-01

Griseti E, Bello AA, Bieth E, et al (2023)

Molecular mechanisms of perilipin protein function in lipid droplet metabolism.

FEBS letters [Epub ahead of print].

Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar domain organization: an amino-terminal PAT domain and an 11-mer repeat region, which can fold into amphipathic helices that interact with LDs, followed by a structured carboxy-terminal domain. Variations of this organization that arose during vertebrate evolution allow for functional specialization between perilipins in relation to the metabolic needs of different tissues. We discuss how different features of perilipins influence their interaction with LDs and their cellular targeting. PLIN1 and PLIN5 play a direct role in lipolysis by regulating the recruitment of lipases to LDs and LD interaction with mitochondria. Other perilipins, particularly PLIN2, appear to protect LDs from lipolysis, but the molecular mechanism is not clear. PLIN4 stands out with its long repetitive region, whereas PLIN3 is most widely expressed and is used as a nascent LD marker. Finally, we discuss the genetic variability in perilipins in connection with metabolic disease, prominent for PLIN1 and PLIN4, underlying the importance of understanding the molecular function of perilipins.

RevDate: 2024-01-02
CmpDate: 2023-12-25

He X, Zhang X, Deng Y, et al (2023)

Structural Reorganization in Two Alfalfa Mitochondrial Genome Assemblies and Mitochondrial Evolution in Medicago Species.

International journal of molecular sciences, 24(24):.

Plant mitochondria are crucial for species evolution, phylogenetics, classification, and identification as maternal genetic material. However, the presence of numerous repetitive sequences, complex structures, and a low number of genes in the mitochondrial genome has hindered its complete assembly and related research endeavors. In this study, we assembled two mitochondrial genomes of alfalfa varieties of Zhongmu No.1 (299,123 bp) and Zhongmu No.4 (306,983 bp), based on a combination of PacBio, Illumina, and Hi-C sequences. The comparison of genome assemblies revealed that the same number of mitochondrial genes, including thirty-three protein-coding genes, sixteen tRNA genes, and three rRNA genes existed in the two varieties. Additionally, large fragments of repetitive sequences were found underlying frequent mitochondrial recombination events. We observed extensive transfer of mitochondrial fragments into the nuclear genome of Zhongmu No.4. Analysis of the cox1 and rrn18s genes in 35 Medicago accessions revealed the presence of population-level deletions and substitutions in the rrn18s gene. We propose that mitochondrial structural reorganizations may contribute to alfalfa evolution.

RevDate: 2024-01-11
CmpDate: 2024-01-11

Uvizl M, Puechmaille SJ, Power S, et al (2024)

Comparative Genome Microsynteny Illuminates the Fast Evolution of Nuclear Mitochondrial Segments (NUMTs) in Mammals.

Molecular biology and evolution, 41(1):.

The escape of DNA from mitochondria into the nuclear genome (nuclear mitochondrial DNA, NUMT) is an ongoing process. Although pervasively observed in eukaryotic genomes, their evolutionary trajectories in a mammal-wide context are poorly understood. The main challenge lies in the orthology assignment of NUMTs across species due to their fast evolution and chromosomal rearrangements over the past 200 million years. To address this issue, we systematically investigated the characteristics of NUMT insertions in 45 mammalian genomes and established a novel, synteny-based method to accurately predict orthologous NUMTs and ascertain their evolution across mammals. With a series of comparative analyses across taxa, we revealed that NUMTs may originate from nonrandom regions in mtDNA, are likely found in transposon-rich and intergenic regions, and unlikely code for functional proteins. Using our synteny-based approach, we leveraged 630 pairwise comparisons of genome-wide microsynteny and predicted the NUMT orthology relationships across 36 mammals. With the phylogenetic patterns of NUMT presence-and-absence across taxa, we constructed the ancestral state of NUMTs given the mammal tree using a coalescent method. We found support on the ancestral node of Fereuungulata within Laurasiatheria, whose subordinal relationships are still controversial. This study broadens our knowledge on NUMT insertion and evolution in mammalian genomes and highlights the merit of NUMTs as alternative genetic markers in phylogenetic inference.

RevDate: 2023-12-23
CmpDate: 2023-12-22

Cui Z, Zhong Y, Sun Z, et al (2023)

Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica.

Nature communications, 14(1):8480.

Succinic acid (SA) is an important C4-dicarboxylic acid. Microbial production of SA at low pH results in low purification costs and hence good overall process economics. However, redox imbalances limited SA biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, we engineer the strictly aerobic yeast Yarrowia lipolytica for efficient SA production without pH control. Introduction of the reductive TCA cycle into the cytosol of a succinate dehydrogenase-disrupted yeast strain causes arrested cell growth. Although adaptive laboratory evolution restores cell growth, limited NADH supply restricts SA production. Reconfiguration of the reductive SA biosynthesis pathway in the mitochondria through coupling the oxidative and reductive TCA cycle for NADH regeneration results in improved SA production. In pilot-scale fermentation, the engineered strain produces 111.9 g/L SA with a yield of 0.79 g/g glucose within 62 h. This study paves the way for industrial production of biobased SA.

RevDate: 2023-12-19

He Z, Fang Y, Zhang F, et al (2023)

Adenine nucleotide translocase 2 (Ant2) is required for individualization of spermatogenesis of Drosophila melanogaster.

Insect science [Epub ahead of print].

Successful completion of spermatogenesis is crucial for the perpetuation of the species. In Drosophila, spermatid individualization, a process involving changes in mitochondrial structure and function is critical to produce functional mature sperm. Ant2, encoding a mitochondrial adenine nucleotide translocase, is highly expressed in male testes and plays a role in energy metabolism in the mitochondria. However, its molecular function remains unclear. Here, we identified an important role of Ant2 in spermatid individualization. In Ant2 knockdown testes, spermatid individualization complexes composed of F-actin cones exhibited a diffuse distribution, and mature sperms were absent in the seminal vesicle, thus leading to male sterility. The most striking effects in Ant2-knockdown spermatids were decrease in tubulin polyglycylation and disruption of proper mitochondria derivatives function. Excessive apoptotic cells were also observed in Ant2-knockdown testes. To further investigate the phenotype of Ant2 knockdown in testes at the molecular level, complementary transcriptome and proteome analyses were performed. At the mRNA level, 868 differentially expressed genes were identified, of which 229 genes were upregulated and 639 were downregulated induced via Ant2 knockdown. iTRAQ-labeling proteome analysis revealed 350 differentially expressed proteins, of which 117 proteins were upregulated and 233 were downregulated. The expression of glutathione transferase (GstD5, GstE5, GstE8, and GstD3), proteins involved in reproduction were significantly regulated at both the mRNA and protein levels. These results indicate that Ant2 is crucial for spermatid maturation by affecting mitochondrial morphogenesis.

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