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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 25 Oct 2021 at 01:50 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 pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2021-10-21
CmpDate: 2021-10-21

Horoiwa M, Mandagi IF, Sutra N, et al (2021)

Mitochondrial introgression by ancient admixture between two distant lacustrine fishes in Sulawesi Island.

PloS one, 16(6):e0245316.

Sulawesi, an island located in a biogeographical transition zone between Indomalaya and Australasia, is famous for its high levels of endemism. Ricefishes (family Adrianichthyidae) are an example of taxa that have uniquely diversified on this island. It was demonstrated that habitat fragmentation due to the Pliocene juxtaposition among tectonic subdivisions of this island was the primary factor that promoted their divergence; however, it is also equally probable that habitat fusions and resultant admixtures between phylogenetically distant species may have frequently occurred. Previous studies revealed that some individuals of Oryzias sarasinorum endemic to a tectonic lake in central Sulawesi have mitochondrial haplotypes that are similar to the haplotypes of O. eversi, which is a phylogenetically related but geologically distant (ca. 190 km apart) adrianichthyid endemic to a small fountain. In this study, we tested if this reflects ancient admixture of O. eversi and O. sarasinorum. Population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that O. eversi and O. sarasinorum are substantially reproductively isolated from each other. Comparison of demographic models revealed that the models assuming ancient admixture from O. eversi to O. sarasinorum was more supported than the models assuming no admixture; this supported the idea that the O. eversi-like mitochondrial haplotype in O. sarasinorum was introgressed from O. eversi. This study is the first to demonstrate ancient admixture of lacustrine or pond organisms in Sulawesi beyond 100 km. The complex geological history of this island enabled such island-wide admixture of lacustrine organisms, which usually experience limited migration.

RevDate: 2021-10-21
CmpDate: 2021-10-21

Fajardo RG, Fariña FO, Rey AM, et al (2021)

Relationship Between the Dynamics of Telomere Loss in Peripheral Blood Leukocytes From Knee Osteoarthritis Patients and Mitochondrial DNA Haplogroups.

The Journal of rheumatology, 48(10):1603-1607.

OBJECTIVE: To evaluate the evolution of telomere length from peripheral blood leukocytes (PBLs) in subjects from the Osteoarthritis Initiative (OAI) cohort in relation to the incidence of osteoarthritis (OA), and to explore its possible interactive influence with the mitochondrial DNA (mtDNA) haplogroup.

METHODS: Dynamics of telomere sequence loss were quantified in PBLs from initially healthy individuals (without symptoms or radiological signs), 78 carrying the mtDNA cluster HV, and 47 with cluster JT, from the OAI, during a 72-month follow-up period. The incidence of knee OA during this period (n = 39) was radiographically established when Kellgren-Lawrence (KL) score increased from < 2 at recruitment, to ≥ 2 at the end of 72 months of follow-up. Multivariate analysis using binary logistic regression was performed to assess PBL telomere loss and mtDNA haplogroups as associated risk factors of incidence of knee OA.

RESULTS: Carriers of cluster HV showed knee OA incidence twice that of the JT carriers (n = 30 vs 9). The rate of PBL telomere loss was higher in cluster HV carriers and in individuals with incident knee OA. Multivariate analysis showed that the dynamics of PBL telomere shortening can be a consistent risk marker of knee OA incidence. Subjects with nonincident knee OA showed a slower telomere loss than those with incident knee OA; the difference was more significant in carriers of cluster JT than in HV.

CONCLUSION: An increased rate of telomere loss in PBLs may reflect a systemic accelerated senescence phenotype that could be potentiated by the mitochondrial function, increasing the susceptibility of developing knee OA.

RevDate: 2021-10-20

Fan Y, Asao S, Furbank RT, et al (2021)

The crucial roles of mitochondria in supporting C4 photosynthesis.

The New phytologist [Epub ahead of print].

C4 photosynthesis involves a series of biochemical and anatomical traits that significantly improve plant productivity under conditions that reduce the efficiency of C3 photosynthesis. We explore how evolution of the three classical biochemical types of C4 photosynthesis (NADP-ME, NAD-ME and PCK types) has affected the functions and properties of mitochondria. Mitochondria in C4 NAD-ME and PCK types play a direct role in decarboxylation of metabolites for C4 photosynthesis. Mitochondria in C4 PCK type also provide ATP for C4 metabolism, although this role for ATP provision is not seen in NAD-ME type. Such involvement has increased mitochondrial abundance/size and associated enzymatic capacity, and has altered mitochondrial location, ultrastructure and role in cellular carbon metabolism in the NAD-ME and PCK types. By contrast, these changes in mitochondrial properties are absent in the C4 NADP-ME type and C3 leaves, where mitochondria play no direct role in photosynthesis. From an eco-physiological perspective, rates of leaf respiration in darkness vary considerably among C4 species but does not differ systematically among the three C4 types. This review outlines further mitochondrial research in key areas central to the engineering of C4 pathway into C3 plants and to the understanding of variation in rates of C4 dark respiration.

RevDate: 2021-10-19

Lim HJ, Yoon H, Kim H, et al (2021)

Extracellular Vesicle Proteomes Shed Light on the Evolutionary, Interactive, and Functional Divergence of Their Biogenesis Mechanisms.

Frontiers in cell and developmental biology, 9:734950.

Extracellular vesicles (EVs) are membranous structures containing bioactive molecules, secreted by most cells into the extracellular environment. EVs are classified by their biogenesis mechanisms into two major subtypes: ectosomes (enriched in large EVs; lEVs), budding directly from the plasma membrane, which is common in both prokaryotes and eukaryotes, and exosomes (enriched in small EVs; sEVs) generated through the multivesicular bodies via the endomembrane system, which is unique to eukaryotes. Even though recent proteomic analyses have identified key proteins associated with EV subtypes, there has been no systematic analysis, thus far, to support the general validity and utility of current EV subtype separation methods, still largely dependent on physical properties, such as vesicular size and sedimentation. Here, we classified human EV proteomic datasets into two main categories based on distinct centrifugation protocols commonly used for isolating sEV or lEV fractions. We found characteristic, evolutionarily conserved profiles of sEV and lEV proteins linked to their respective biogenetic origins. This may suggest that the evolutionary trajectory of vesicular proteins may result in a membership bias toward specific EV subtypes. Protein-protein interaction (PPI) network analysis showed that vesicular proteins formed distinct clusters with proteins in the same EV fraction, providing evidence for the existence of EV subtype-specific protein recruiters. Moreover, we identified functional modules enriched in each fraction, including multivesicular body sorting for sEV, and mitochondria cellular respiration for lEV proteins. Our analysis successfully captured novel features of EVs embedded in heterogeneous proteomics studies and suggests specific protein markers and signatures to be used as quality controllers in the isolation procedure for subtype-enriched EV fractions.

RevDate: 2021-10-16

do Amaral MJ, de Andrade Rosa I, Andrade SA, et al (2021)

The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles.

Biochimica et biophysica acta. Molecular cell research pii:S0167-4889(21)00215-9 [Epub ahead of print].

Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step toward understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent.

RevDate: 2021-10-18
CmpDate: 2021-10-18

Yap KN, Y Zhang (2021)

Revisiting the question of nucleated versus enucleated erythrocytes in birds and mammals.

American journal of physiology. Regulatory, integrative and comparative physiology, 321(4):R547-R557.

Erythrocyte enucleation is thought to have evolved in mammals to support their energetic cost of high metabolic activities. However, birds face similar selection pressure yet possess nucleated erythrocytes. Current hypotheses on the mammalian erythrocyte enucleation claim that the absence of cell organelles allows erythrocytes to 1) pack more hemoglobin into the cells to increase oxygen carrying capacity and 2) decrease erythrocyte size for increased surface area-to-volume ratio, and improved ability to traverse small capillaries. In this article, we first empirically tested current hypotheses using both conventional and phylogenetically informed analysis comparing literature values of mean cell hemoglobin concentration (MCHC) and mean cell volume (MCV) between 181 avian and 194 mammalian species. We found no difference in MCHC levels between birds and mammals using both conventional and phylogenetically corrected analysis. MCV was higher in birds than mammals according to conventional analysis, but the difference was lost when we controlled for phylogeny. These results suggested that avian and mammalian erythrocytes may employ different strategies to solve a common problem. To further investigate existing hypotheses or develop new hypothesis, we need to understand the functions of various organelles in avian erythrocytes. Consequently, we covered potential physiological functions of various cell organelles in avian erythrocytes based on current knowledge, while making explicit comparisons with their mammalian counterparts. Finally, we proposed by taking an integrative and comparative approach, using tools from molecular biology to evolutionary biology, would allow us to better understand the fundamental physiological functions of various components of avian and mammalian erythrocytes.

RevDate: 2021-10-19
CmpDate: 2021-10-19

Singh L, Atilano SR, Jager MJ, et al (2021)

Mitochondrial DNA polymorphisms and biogenesis genes in primary and metastatic uveal melanoma cell lines.

Cancer genetics, 256-257:91-99.

PURPOSE: This study was designed to identify mitochondrial (mt) DNA variations in primary and metastatic uveal melanoma (UM) cell lines and their relation with cell metabolism to gain insight into metastatic progression.

METHOD: The entire mtDNA genomes were sequenced using Sanger sequencing from two primary UM cell lines (92.1 and MEL270) and two cell lines (OMM2.3 and OMM2.5) derived from liver metastases of the MEL270 patient. The mtDNA copy numbers determined by the ratio of nDNA versus mtDNA. qRT-PCR was used to evaluate expression levels of mitochondrial biogenesis genes.

RESULTS: Sequencing showed that cell line MEL270 and metastases-derived OMM2.3 and OMM2.5 cell lines had homoplasmic single nucleotide polymorphisms (SNPs) representing J1c7a haplogroup, whereas 92.1 cells had mtDNA H31a haplogroup. mtDNA copy numbers were significantly higher in primary cell lines. The metastatic UM cells showed down-regulation of POLG, TFAM, NRF-1 and SIRT1 compared to their primary MEL270 cells. PGC-1α was downregulated in 92.1 and upregulated in MEL270, OMM2.3 and OMM2.5.

CONCLUSIONS: Our finding suggests that within metastatic cells, the heteroplasmic SNPs, copy numbers and mitochondrial biogenesis genes are modulated differentially compared to their primary UM cells. Therefore, investigating pathogenic mtDNA variants associated with cancer metabolic susceptibility may provide future therapeutic strategies in metastatic UM.

RevDate: 2021-10-20
CmpDate: 2021-10-20

Cai C, Gu K, Zhao H, et al (2021)

Screening and verification of extranuclear genetic markers in green tide algae from the Yellow Sea.

PloS one, 16(6):e0250968.

Over the past decade, Ulva compressa, a cosmopolitan green algal species, has been identified as a component of green tides in the Yellow Sea, China. In the present study, we sequenced and annotated the complete chloroplast genome of U. compressa (alpha-numeric code: RD9023) and focused on the assessment of genome length, homology, gene order and direction, intron size, selection strength, and substitution rate. We compared the chloroplast genome with the mitogenome. The generated phylogenetic tree was analyzed based on single and aligned genes in the chloroplast genome of Ulva compared to mitogenome genes to detect evolutionary trends. U. compressa and U. mutabilis chloroplast genomes had similar gene queues, with individual genes exhibiting high homology levels. Chloroplast genomes were clustered together in the entire phylogenetic tree and shared several forward/palindromic/tandem repetitions, similar to those in U. prolifera and U. linza. However, U. fasciata and U. ohnoi were more divergent, especially in sharing complementary/palindromic repetitions. In addition, phylogenetic analyses of the aligned genes from their chloroplast genomes and mitogenomes confirmed the evolutionary trends of the extranuclear genomes. From phylogenetic analysis, we identified the petA chloroplast genes as potential genetic markers that are similar to the tufA marker. Complementary/forward/palindromic interval repetitions were more abundant in chloroplast genomes than in mitogenomes. Interestingly, a few tandem repetitions were significant for some Ulva subspecies and relatively more evident in mitochondria than in chloroplasts. Finally, the tandem repetition [GAAATATATAATAATA × 3, abbreviated as TRg)] was identified in the mitogenome of U. compressa and the conspecific strain U. mutabilis but not in other algal species of the Yellow Sea. Owing to the high morphological plasticity of U. compressa, the findings of this study have implications for the rapid non-sequencing detection of this species during the occurrence of green tides in the region.

RevDate: 2021-10-20
CmpDate: 2021-10-20

Tuda M, Iwase SI, Kébé K, et al (2021)

Diversification, selective sweep, and body size in the invasive Palearctic alfalfa weevil infected with Wolbachia.

Scientific reports, 11(1):9664.

The alfalfa weevil Hypera postica, native to the Western Palearctic, is an invasive legume pest with two divergent mitochondrial clades in its invading regions, the Western clade and the Eastern/Egyptian clade. However, knowledge regarding the native populations is limited. The Western clade is infected with the endosymbiotic bacteria Wolbachia that cause cytoplasmic incompatibility in host weevils. Our aim was to elucidate the spatial genetic structure of this insect and the effect of Wolbachia on its population diversity. We analyzed two mitochondrial and two nuclear genes of the weevil from its native ranges. The Western clade was distributed in western/central Europe, whereas the Eastern/Egyptian clade was distributed from the Mediterranean basin to central Asia. Intermediate mitotypes were found from the Balkans to central Asia. Most Western clade individuals in western Europe were infected with an identical Wolbachia strain. Mitochondrial genetic diversity of the infected individuals was minimal. The infected clades demonstrated a higher nonsynonymous/synonymous substitution rate ratio than the uninfected clades, suggesting a higher fixation of nonsynonymous mutations due to a selective sweep by Wolbachia. Trans-Mediterranean and within-European dispersal routes were supported. We suggest that the ancestral populations diversified by geographic isolation due to glaciations and that the diversity was reduced in the west by a recent Wolbachia-driven sweep(s). The intermediate clade exhibited a body size and host plant that differed from the other clades. Pros and cons of the possible use of infected-clade males to control uninfected populations are discussed.

RevDate: 2021-10-19
CmpDate: 2021-10-19

Caccavale F, Osca D, D'Aniello S, et al (2021)

Molecular taxonomy confirms that the northeastern Atlantic and Mediterranean Sea harbor a single lancelet, Branchiostoma lanceolatum (Pallas, 1774) (Cephalochordata: Leptocardii: Branchiostomatidae).

PloS one, 16(5):e0251358.

Branchiostomatidae (lancelets or amphioxus) comprises about 30 species, several of which are well-established models in evolutionary development. Our zoological and ecological knowledge of the family is nonetheless limited. Despite evident differences can be found among known populations, the taxonomy of Branchiostoma lanceolatum (type species of the genus Branchiostoma) has never been investigated with modern methods through its range in the northeastern Atlantic and Mediterranean Sea. We address this via a multilocus molecular approach and comparing specimens collected from different European populations. Results obtained here confirm the presence of a single species inhabiting the range between the topotypical localities of B. lanceolatum (Atlantic Ocean) and of its junior synonym B. lubricum (Mediterranean Sea), without evincing geographical structure between populations. This suggests that environment most likely drives the characteristics observed in different geographic areas. The long larval phase and the slow mutation rate in lancelets may have played a key role in the evolutionary history of this iconic species.

RevDate: 2021-10-19
CmpDate: 2021-10-19

Wood AW, TF Duda (Jr) (2021)

Reticulate evolution in Conidae: Evidence of nuclear and mitochondrial introgression.

Molecular phylogenetics and evolution, 161:107182.

Conidae is a hyperdiverse family of marine snails that has many hallmarks of adaptive radiation. Hybridization and introgression may contribute to such instances of rapid diversification by generating novel gene combinations that facilitate exploitation of distinct niches. Here we evaluated whether or not these mechanisms may have contributed to the evolutionary history of a subgenus of Conidae (Virroconus). Several observations hint at evidence of past introgression for members of this group, including incongruence between phylogenetic relationships inferred from mitochondrial gene sequences and morphology and widespread sympatry of many Virroconus species in the Indo-West Pacific. We generated and analyzed transcriptome data of Virroconus species to (i) infer a robust nuclear phylogeny, (ii) assess mitochondrial and nuclear gene tree discordance, and (iii) formally test for introgression of nuclear loci. We identified introgression of mitochondrial genomes and nuclear gene regions between ancestors of one pair of Virroconus species, and mitochondrial introgression between another pair. We also found evidence of adaptive introgression of conotoxin venom loci between a third pair of species. Together, our results demonstrate that hybridization and introgression impacted the evolutionary history of Virroconus and hence may have contributed to the adaptive radiation of Conidae.

RevDate: 2021-10-19
CmpDate: 2021-10-19

Bober S, Glaubrecht M, Hausdorf B, et al (2021)

One, two or three? Integrative species delimitation of short-range endemic Hemicycla species (Gastropoda: Helicidae) from the Canary Islands based on morphology, barcoding, AFLP and ddRADseq data.

Molecular phylogenetics and evolution, 161:107153.

Hemicycla mascaensis and H. diegoi are short-range endemics that occur allopatrically in small areas in the Teno Mountains in the western part of Tenerife (Canary Islands). Both taxa have been recognised as distinct species based on differences in shell morphology and genital anatomy. Preliminary molecular analyses using mitochondrial markers suggested a potential paraphyly of H. diegoi with regard to H. mascaensis. We here use multilocus AFLP data and ddRADseq data as well as distribution data, data on shell morphology and genital anatomy to assess the status of these taxa using phylogenetic analyses, species tree reconstruction and molecular species delimitation based on the multispecies coalescent as implemented in BFD* and BPP in an integrative approach. Our analyses show that, based on the analysis of multilocus data, the two taxa are reciprocally monophyletic. Species delimitation methods, however, tend to recognise all investigated populations as distinct species, albeit neither lending unambiguous support to any of the species hypotheses. The comparison of the anatomy of distal genital organs further suggests differentiation within H. mascaensis. This highlights the need for a balanced weighting of arguments from different lines of evidence to determine species status and calls for cautious interpretations of the results of molecular species delimitation analyses, especially in organisms with low active dispersal capacities and expected distinct population structuring such as land snails. Taking all available evidence into account, we favour to recognise H. mascaensis and H. diegoi as distinct species, acknowledging, though, that the recognition of both taxa as subspecies (with possibly a third yet undescribed) would also be an option as morphological differentiation is within the limits of other land snail species that are traditionally subdivided into subspecies.

RevDate: 2021-10-15
CmpDate: 2021-10-15

Trefts E, RJ Shaw (2021)

AMPK: restoring metabolic homeostasis over space and time.

Molecular cell, 81(18):3677-3690.

The evolution of AMPK and its homologs enabled exquisite responsivity and control of cellular energetic homeostasis. Recent work has been critical in establishing the mechanisms that determine AMPK activity, novel targets of AMPK action, and the distribution of AMPK-mediated control networks across the cellular landscape. The role of AMPK as a hub of metabolic control has led to intense interest in pharmacologic activation as a therapeutic avenue for a number of disease states, including obesity, diabetes, and cancer. As such, critical work on the compartmentalization of AMPK, its downstream targets, and the systems it influences has progressed in recent years. The variegated distribution of AMPK-mediated control of metabolic homeostasis has revealed key insights into AMPK in normal biology and future directions for AMPK-based therapeutic strategies.

RevDate: 2021-10-13
CmpDate: 2021-10-13

Bilcke G, Osuna-Cruz CM, Santana Silva M, et al (2021)

Diurnal transcript profiling of the diatom Seminavis robusta reveals adaptations to a benthic lifestyle.

The Plant journal : for cell and molecular biology, 107(1):315-336.

Coastal regions contribute an estimated 20% of annual gross primary production in the oceans, despite occupying only 0.03% of their surface area. Diatoms frequently dominate coastal sediments, where they experience large variations in light regime resulting from the interplay of diurnal and tidal cycles. Here, we report on an extensive diurnal transcript profiling experiment of the motile benthic diatom Seminavis robusta. Nearly 90% (23 328) of expressed protein-coding genes and 66.9% (1124) of expressed long intergenic non-coding RNAs showed significant expression oscillations and are predominantly phasing at night with a periodicity of 24 h. Phylostratigraphic analysis found that rhythmic genes are enriched in highly conserved genes, while diatom-specific genes are predominantly associated with midnight expression. Integration of genetic and physiological cell cycle markers with silica depletion data revealed potential new silica cell wall-associated gene families specific to diatoms. Additionally, we observed 1752 genes with a remarkable semidiurnal (12-h) periodicity, while the expansion of putative circadian transcription factors may reflect adaptations to cope with highly unpredictable external conditions. Taken together, our results provide new insights into the adaptations of diatoms to the benthic environment and serve as a valuable resource for the study of diurnal regulation in photosynthetic eukaryotes.

RevDate: 2021-10-12
CmpDate: 2021-10-12

Liu Y, Yao L, Ci Y, et al (2021)

Genetic differentiation of geographic populations of Rattus tanezumi based on the mitochondrial Cytb gene.

PloS one, 16(3):e0248102.

Rattus tanezumi is a common domestic rat and host of the bubonic plague pathogen in China and Southeast Asia (SEA). The origin, genetic differentiation and dispersal of R. tanezumi have received increasing attention from researchers. The population genetics of R. tanezumi based on its mitochondrial cytochrome b gene have been studied to explain the origin, relationships and dispersal of populations. In this study, we captured a total of 229 rats; morphological and molecular biological identification cytochrome oxidase subunit I (COI) confirmed 131 R. tanezumi individuals collected from 6 provincial areas, and their Cytb gene sequences were analyzed. The results showed that the population in Mohan (MH), Yunnan, had the highest genetic diversity, while that in Ningde (ND), Fujian, had the lowest. Tajima's D statistic for all populations was negative and nonsignificant, indicating the possible expansion of R. tanezumi populations. Low gene flow occurred between the Zhangmu (ZM) R. tanezumi population and other populations, and the genetic differentiation among them was high. Furthermore, our analyses revealed the ZM lineage was the oldest lineage among the groups and diverged ~1.06 Mya, followed by the Luoyang (LY) lineages (~0.51 Mya) and Yunnan lineage (~0.33 Mya). In southeastern Yunnan, the Jinshuihe (JSH) and MH populations were more closely related to the populations in southeastern China (Fuzhou (FZ), ND, Quanzhou (QZ), Nanchang (NC)) and inland areas (Chongqing (CQ), LY) than to those in other areas of Yunnan (Jiegao (JG) and Qingshuihe (QSH)), indicating that R. tanezumi may have spread from southeastern Yunnan to the interior of China. In summary, R. tanezumi may have originated in ZM and adjacent areas, spread to Yunnan, and then spread from the southeast of Yunnan inland or directly eastward from ZM to inland China.

RevDate: 2021-10-12
CmpDate: 2021-10-12

Gladyck S, Aras S, Hüttemann M, et al (2021)

Regulation of COX Assembly and Function by Twin CX9C Proteins-Implications for Human Disease.

Cells, 10(2):.

Oxidative phosphorylation is a tightly regulated process in mammals that takes place in and across the inner mitochondrial membrane and consists of the electron transport chain and ATP synthase. Complex IV, or cytochrome c oxidase (COX), is the terminal enzyme of the electron transport chain, responsible for accepting electrons from cytochrome c, pumping protons to contribute to the gradient utilized by ATP synthase to produce ATP, and reducing oxygen to water. As such, COX is tightly regulated through numerous mechanisms including protein-protein interactions. The twin CX9C family of proteins has recently been shown to be involved in COX regulation by assisting with complex assembly, biogenesis, and activity. The twin CX9C motif allows for the import of these proteins into the intermembrane space of the mitochondria using the redox import machinery of Mia40/CHCHD4. Studies have shown that knockdown of the proteins discussed in this review results in decreased or completely deficient aerobic respiration in experimental models ranging from yeast to human cells, as the proteins are conserved across species. This article highlights and discusses the importance of COX regulation by twin CX9C proteins in the mitochondria via COX assembly and control of its activity through protein-protein interactions, which is further modulated by cell signaling pathways. Interestingly, select members of the CX9C protein family, including MNRR1 and CHCHD10, show a novel feature in that they not only localize to the mitochondria but also to the nucleus, where they mediate oxygen- and stress-induced transcriptional regulation, opening a new view of mitochondrial-nuclear crosstalk and its involvement in human disease.

RevDate: 2021-10-11

Valera-Calero JA, Úbeda-D'Ocasar E, Caballero-Corella M, et al (2021)

Cervical Multifidus Morphology and Quality is not Associated with Clinical Variables in Women with Fibromyalgia: An Observational Study.

Pain medicine (Malden, Mass.) pii:6388048 [Epub ahead of print].

OBJECTIVE: Some studies have reported the presence of histological alterations such as myofibers disorganization and abnormalities in the number and shape of mitochondria in patients with fibromyalgia syndrome (FMS). Although Ultrasound imaging (US) is used to quantitatively characterize muscle tissues, US studies in patients with FMS are lacking. Therefore, we aimed to describe morphological and qualitative cervical multifidus (CM) muscle US features in women with FMS and to assess their correlation with clinical indicators.

DESIGN: Observational study.

SETTING: AFINSYFACRO Fibromyalgia Association (Madrid, Spain).

SUBJECTS: Forty-five women with FMS participated.

METHODS: Sociodemographic (e.g., age, height, weight, and BMI), clinical (e.g., pain -NPRS-, evolution time, related-disability -FIQ-) outcomes were collected. Images were acquired bilaterally at the cervical spine (C4-C5 level) and measured by an experienced examiner for assessing muscle morphology (e.g., cross-sectional area -CSA-, perimeter and shape) and quality (mean echo-intensity -EI- and intramuscular fatty infiltration -FI-). Side-to-side comparisons and a correlational analysis were conducted.

RESULTS: No significant side-to-side differences were found for morphology nor quality features (P > 0.05). None of the clinical indicators were associated with US characteristics (all, P > 0.05).

CONCLUSION: Our results showed no side-to-side differences for CM morphology and quality as assessed with US. No associations between CM muscle morphology nor quality with FIQ, PPT, NPRS nor evolution time were observed. Our preliminary data suggest that muscle morphology is not directly related to pain and related-disability in women with FMS.

RevDate: 2021-10-11
CmpDate: 2021-10-11

Gupta A, Shrivastava D, Shakya AK, et al (2021)

PfKsgA1 functions as a transcription initiation factor and interacts with the N-terminal region of the mitochondrial RNA polymerase of Plasmodium falciparum.

International journal for parasitology, 51(1):23-37.

The small mitochondrial genome (mtDNA) of the malaria parasite is known to transcribe its genes polycistonically, although promoter element(s) have not yet been identified. An unusually large Plasmodium falciparum candidate mitochondrial phage-like RNA polymerase (PfmtRNAP) with an extended N-terminal region is encoded by the parasite nuclear genome. Using specific antibodies against the enzyme, we established that PfmtRNAP was targeted exclusively to the mitochondrion and interacted with mtDNA. Phylogenetic analysis showed that it is part of a separate apicomplexan clade. A search for PfmtRNAP-associated transcription initiation factors using sequence homology and in silico protein-protein interaction network analysis identified PfKsgA1. PfKsgA1 is a dual cytosol- and mitochondrion-targeted protein that functions as a small subunit rRNA dimethyltransferase in ribosome biogenesis. Chromatin immunoprecipitation showed that PfKsgA1 interacts with mtDNA, and in vivo crosslinking and pull-down experiments confirmed PfmtRNAP-PfKsgA1 interaction. The ability of PfKsgA1 to serve as a transcription initiation factor was demonstrated by complementation of yeast mitochondrial transcription factor Mtf1 function in Rpo41-driven in vitro transcription. Pull-down experiments using PfKsgA1 and PfmtRNAP domains indicated that the N-terminal region of PfmtRNAP interacts primarily with the PfKsgA1 C-terminal domain with some contacts being made with the linker and N-terminal domain of PfKsgA1. In the absence of full-length recombinant PfmtRNAP, solution structures of yeast mitochondrial RNA polymerase Rpo41 complexes with Mtf1 or PfKsgA1 were determined by small-angle X-ray scattering. Protein interaction interfaces thus identified matched with those reported earlier for Rpo41-Mtf1 interaction and overlaid with the PfmtRNAP-interfacing region identified experimentally for PfKsgA1. Our results indicate that in addition to a role in mitochondrial ribosome biogenesis, PfKsgA1 has an independent function as a transcription initiation factor for PfmtRNAP.

RevDate: 2021-10-07

Lin R, Xia Y, Liu Y, et al (2021)

Comparative Mitogenomic Analysis and the Evolution of Rhizoctonia solani Anastomosis Groups.

Frontiers in microbiology, 12:707281.

Mitochondria are the major energy source for cell functions. However, for the plant fungal pathogens, mitogenome variations and their roles during the host infection processes remain largely unknown. Rhizoctonia solani, an important soil-borne pathogen, forms different anastomosis groups (AGs) and adapts to a broad range of hosts in nature. Here, we reported three complete mitogenomes of AG1-IA RSIA1, AG1-IB RSIB1, and AG1-IC, and performed a comparative analysis with nine published Rhizoctonia mitogenomes (AG1-IA XN, AG1-IB 7/3/14, AG3, AG4, and five Rhizoctonia sp. mitogenomes). These mitogenomes encoded 15 typical proteins (cox1-3, cob, atp6, atp8-9, nad1-6, nad4L, and rps3) and several LAGLIDADG/GIY-YIG endonucleases with sizes ranging from 109,017 bp (Rhizoctonia sp. SM) to 235,849 bp (AG3). We found that their large sizes were mainly contributed by repeat sequences and genes encoding endonucleases. We identified the complete sequence of the rps3 gene in 10 Rhizoctonia mitogenomes, which contained 14 positively selected sites. Moreover, we inferred a robust maximum-likelihood phylogeny of 32 Basidiomycota mitogenomes, representing that seven R. solani and other five Rhizoctonia sp. lineages formed two parallel branches in Agaricomycotina. The comparative analysis showed that mitogenomes of Basidiomycota pathogens had high GC content and mitogenomes of R. solani had high repeat content. Compared to other strains, the AG1-IC strain had low substitution rates, which may affect its mitochondrial phylogenetic placement in the R. solani clade. Additionally, with the published RNA-seq data, we investigated gene expression patterns from different AGs during host infection stages. The expressed genes from AG1-IA (host: rice) and AG3 (host: potato) mainly formed four groups by k-mean partitioning analysis. However, conserved genes represented varied expression patterns, and only the patterns of rps3-nad2 and nad1-m3g18/mag28 (an LAGLIDADG endonuclease) were conserved in AG1-IA and AG3 as shown by the correlation coefficient analysis, suggesting regulation of gene repertoires adapting to infect varied hosts. The results of variations in mitogenome characteristics and the gene substitution rates and expression patterns may provide insights into the evolution of R. solani mitogenomes.

RevDate: 2021-10-06

Evans BJ, Peter BM, Melnick DJ, et al (2021)

Mitonuclear interactions and introgression genomics of macaque monkeys (Macaca) highlight the influence of behaviour on genome evolution.

Proceedings. Biological sciences, 288(1960):20211756.

In most macaques, females are philopatric and males migrate from their natal ranges, which results in pronounced divergence of mitochondrial genomes within and among species. We therefore predicted that some nuclear genes would have to acquire compensatory mutations to preserve compatibility with diverged interaction partners from the mitochondria. We additionally expected that these sex-differences would have distinctive effects on gene flow in the X and autosomes. Using new genomic data from 29 individuals from eight species of Southeast Asian macaque, we identified evidence of natural selection associated with mitonuclear interactions, including extreme outliers of interspecies differentiation and metrics of positive selection, low intraspecies polymorphism and atypically long runs of homozygosity associated with nuclear-encoded genes that interact with mitochondria-encoded genes. In one individual with introgressed mitochondria, we detected a small but significant enrichment of autosomal introgression blocks from the source species of her mitochondria that contained genes which interact with mitochondria-encoded loci. Our analyses also demonstrate that sex-specific demography sculpts genetic exchange across multiple species boundaries. These findings show that behaviour can have profound but indirect effects on genome evolution by influencing how interacting components of different genomic compartments (mitochondria, the autosomes and the sex chromosomes) move through time and space.

RevDate: 2021-10-06
CmpDate: 2021-10-06

Cortassa S, Juhaszova M, Aon MA, et al (2021)

Mitochondrial Ca2+, redox environment and ROS emission in heart failure: Two sides of the same coin?.

Journal of molecular and cellular cardiology, 151:113-125.

Heart failure (HF) is a progressive, debilitating condition characterized, in part, by altered ionic equilibria, increased ROS production and impaired cellular energy metabolism, contributing to variable profiles of systolic and diastolic dysfunction with significant functional limitations and risk of premature death. We summarize current knowledge concerning changes of intracellular Na+ and Ca2+ control mechanisms during the disease progression and their consequences on mitochondrial Ca2+ homeostasis and the shift in redox balance. Absent existing biological data, our computational modeling studies advance a new 'in silico' analysis to reconcile existing opposing views, based on different experimental HF models, regarding variations in mitochondrial Ca2+ concentration that participate in triggering and perpetuating oxidative stress in the failing heart and their impact on cardiac energetics. In agreement with our hypothesis and the literature, model simulations demonstrate the possibility that the heart's redox status together with cytoplasmic Na+ concentrations act as regulators of mitochondrial Ca2+ levels in HF and of the bioenergetics response that will ultimately drive ATP supply and oxidative stress. The resulting model predictions propose future directions to study the evolution of HF as well as other types of heart disease, and to develop novel testable mechanistic hypotheses that may lead to improved therapeutics.

RevDate: 2021-10-05
CmpDate: 2021-10-05

Baleva MV, Piunova UE, Chicherin IV, et al (2021)

Yeast Translational Activator Mss51p and Human ZMYND17 - Two Proteins with a Common Origin, but Different Functions.

Biochemistry. Biokhimiia, 86(9):1151-1161.

Despite its similarity to protein biosynthesis in bacteria, translation in the mitochondria of modern eukaryotes has several unique features, such as the necessity for coordination of translation of mitochondrial mRNAs encoding proteins of the electron transport chain complexes with translation of other protein components of these complexes in the cytosol. In the mitochondria of baker's yeast Saccharomyces cerevisiae, this coordination is carried out by a system of translational activators that predominantly interact with the 5'-untranslated regions of mitochondrial mRNAs. No such system has been found in human mitochondria, except a single identified translational activator, TACO1. Here, we studied the role of the ZMYND17 gene, an ortholog of the yeast gene for the translational activator Mss51p, on the mitochondrial translation in human cells. Deletion of the ZMYND17 gene did not affect translation in the mitochondria, but led to the decrease in the cytochrome c oxidase activity and increase in the amount of free F1 subunit of ATP synthase. We also investigated the evolutionary history of Mss51p and ZMYND17 and suggested a possible mechanism for the divergence of functions of these orthologous proteins.

RevDate: 2021-10-04

Rodríguez E, Grover Thomas F, Camus MF, et al (2021)

Mitonuclear Interactions Produce Diverging Responses to Mild Stress in Drosophila Larvae.

Frontiers in genetics, 12:734255.

Mitochondrial function depends on direct interactions between respiratory proteins encoded by genes in two genomes, mitochondrial and nuclear, which evolve in very different ways. Serious incompatibilities between these genomes can have severe effects on development, fitness and viability. The effect of subtle mitonuclear mismatches has received less attention, especially when subject to mild physiological stress. Here, we investigate how two distinct physiological stresses, metabolic stress (high-protein diet) and redox stress [the glutathione precursor N-acetyl cysteine (NAC)], affect development time, egg-to-adult viability, and the mitochondrial physiology of Drosophila larvae with an isogenic nuclear background set against three mitochondrial DNA (mtDNA) haplotypes: one coevolved (WT) and two slightly mismatched (COX and BAR). Larvae fed the high-protein diet developed faster and had greater viability in all haplotypes. The opposite was true of NAC-fed flies, especially those with the COX haplotype. Unexpectedly, the slightly mismatched BAR larvae developed fastest and were the most viable on both treatments, as well as control diets. These changes in larval development were linked to a shift to complex I-driven mitochondrial respiration in all haplotypes on the high-protein diet. In contrast, NAC increased respiration in COX larvae but drove a shift toward oxidation of proline and succinate. The flux of reactive oxygen species was increased in COX larvae treated with NAC and was associated with an increase in mtDNA copy number. Our results support the notion that subtle mitonuclear mismatches can lead to diverging responses to mild physiological stress, undermining fitness in some cases, but surprisingly improving outcomes in other ostensibly mismatched fly lines.

RevDate: 2021-10-04
CmpDate: 2021-10-04

Kelley JL, Desvignes T, McGowan KL, et al (2021)

microRNA expression variation as a potential molecular mechanism contributing to adaptation to hydrogen sulphide.

Journal of evolutionary biology, 34(6):977-988.

microRNAs (miRNAs) are post-transcriptional regulators of gene expression and can play an important role in modulating organismal development and physiology in response to environmental stress. However, the role of miRNAs in mediating adaptation to diverse environments in natural study systems remains largely unexplored. Here, we characterized miRNAs and their expression in Poecilia mexicana, a species of small fish that inhabits both normal streams and extreme environments in the form of springs rich in toxic hydrogen sulphide (H2 S). We found that P. mexicana has a similar number of miRNA genes as other teleosts. In addition, we identified a large population of mature miRNAs that were differentially expressed between locally adapted populations in contrasting habitats, indicating that miRNAs may contribute to P. mexicana adaptation to sulphidic environments. In silico identification of differentially expressed miRNA-mRNA pairs revealed, in the sulphidic environment, the downregulation of miRNAs predicted to target mRNAs involved in sulphide detoxification and cellular homeostasis, which are pathways essential for life in H2 S-rich springs. In addition, we found that predicted targets of upregulated miRNAs act in the mitochondria (16.6% of predicted annotated targets), which is the main site of H2 S toxicity and detoxification, possibly modulating mitochondrial function. Together, the differential regulation of miRNAs between these natural populations suggests that miRNAs may be involved in H2 S adaptation by promoting functions needed for survival and reducing functions affected by H2 S. This study lays the groundwork for further research to directly demonstrate the role of miRNAs in adaptation to H2 S. Overall, this study provides a critical stepping-stone towards a comprehensive understanding of the regulatory mechanisms underlying the adaptive variation in gene expression in a natural system.

RevDate: 2021-10-01
CmpDate: 2021-10-01

Ndosi BA, Park H, Lee D, et al (2021)

Mitochondrial Genome of Spirometra theileri Compared with Other Spirometra Species.

The Korean journal of parasitology, 59(2):139-148.

This study was carried out to provide information on the taxonomic classification and analysis of mitochondrial genomes of Spirometra theileri. One strobila of S. theileri was collected from the intestine of an African leopard (Panthera pardus) in the Maswa Game Reserve, Tanzania. The complete mtDNA sequence of S. theileri was 13,685 bp encoding 36 genes including 12 protein genes, 22 tRNAs and 2 rRNAs with absence of atp8. Divergences of 12 protein-coding genes were as follow: 14.9% between S. theileri and S. erinaceieuropaei, 14.7% between S. theileri and S. decipiens, and 14.5% between S. theileri with S. ranarum. Divergences of 12 proteins of S. theileri and S. erinaceieuropaei ranged from 2.3% in cox1 to 15.7% in nad5, while S. theileri varied from S. decipiens and S. ranarum by 1.3% in cox1 to 15.7% in nad3. Phylogenetic relationship of S. theileri with eucestodes inferred using the maximum likelihood and Bayesian inferences exhibited identical tree topologies. A clade composed of S. decipiens and S. ranarum formed a sister species to S. erinaceieuropaei, and S. theileri formed a sister species to all species in this clade. Within the diphyllobothridean clade, Dibothriocephalus, Diphyllobothrium and Spirometra formed a monophyletic group, and sister genera were well supported.

RevDate: 2021-09-29

Fenton A, Camus MF, GDD Hurst (2021)

Positive selection on mitochondria may eliminate heritable microbes from arthropod populations.

Proceedings. Biological sciences, 288(1959):20211735.

Diverse eukaryotic taxa carry facultative heritable symbionts, microbes that are passed from mother to offspring. These symbionts are coinherited with mitochondria, and selection favouring either new symbionts, or new symbiont variants, is known to drive loss of mitochondrial diversity as a correlated response. More recently, evidence has accumulated of episodic directional selection on mitochondria, but with currently unknown consequences for symbiont evolution. We therefore employed a population genetic mean field framework to model the impact of selection on mitochondrial DNA (mtDNA) upon symbiont frequency for three generic scenarios of host-symbiont interaction. Our models predict that direct selection on mtDNA can drive symbionts out of the population where a positively selected mtDNA mutation occurs initially in an individual that is uninfected with the symbiont, and the symbiont is initially at low frequency. When, by contrast, the positively selected mtDNA mutation occurs in a symbiont-infected individual, the mutation becomes fixed and in doing so removes symbiont variation from the population. We conclude that the molecular evolution of symbionts and mitochondria, which has previously been viewed from a perspective of selection on symbionts driving the evolution of a neutral mtDNA marker, should be reappraised in the light of positive selection on mtDNA.

RevDate: 2021-09-28

Weerth RS, Medlock AE, HA Dailey (2021)

Ironing out the Distribution of [2Fe-2S] Motifs in Ferrochelatases.

The Journal of biological chemistry pii:S0021-9258(21)00819-X [Epub ahead of print].

Heme, a near ubiquitous co-factor, is synthesized by most organisms. The essential step of insertion of iron into the porphyrin macrocycle is mediated by the enzyme ferrochelatase. Several ferrochelatases have been characterized and it has been experimentally shown that a fraction of them contain [2Fe-2S] clusters. It has been suggested that all metazoan ferrochelatases have such clusters, but among bacteria, these clusters have been most commonly identified in Actinobacteria and a few other bacteria. Despite this, the function of the [2Fe-2S] cluster remains undefined. With the large number of sequenced genomes currently available, we comprehensively assessed the distribution of putative [2Fe-2S] clusters throughout the ferrochelatase protein family. We discovered that while rare within the bacterial ferrochelatase family, this cluster is prevalent in a subset of phyla. Of note is that genomic data show that the cluster is not common in Actinobacteria, as is currently thought based on the small number of actinobacterial ferrochelatases experimentally examined. With available physiological data for each genome included, we identified a correlation between the presence of the microbial cluster and aerobic metabolism. Additionally, our analysis suggests that Firmicute ferrochelatases are the most ancient and evolutionarily preceded the Alphaproteobacterial precursor to eukaryotic mitochondria. These findings shed light on distribution and evolution of the [2Fe-2S] cluster in ferrochelatases and will aid in determining the function of the cluster in heme synthesis.

RevDate: 2021-09-28
CmpDate: 2021-09-28

Postic E, Outreman Y, Derocles S, et al (2021)

Genetics of wild and mass-reared populations of a generalist aphid parasitoid and improvement of biological control.

PloS one, 16(4):e0249893.

Due to their ability to parasitize various insect species, generalist parasitoids are widely used as biological control agents. They can be mass-reared and released in agroecosystems to control several pest species in various crops. However, the existence of genetic differentiation among populations of generalist parasitoid species is increasingly recognized and this can be associated with an adaptation to local conditions or to a reduced range of host species. Moreover, constraints of mass-rearing conditions can alter genetic variation within parasitoid populations released. These features could be associated with a reduced efficiency of the control of targeted pest species. Here, we focused on strawberry greenhouses where the control of aphids with the generalist parasitoid Aphidius ervi appears to be inefficient. We investigated whether this inefficiency may have both genetic and ecological bases comparing wild and commercial populations of A. ervi. We used two complementary genetic approaches: one based on the mitochondrial marker COI and one based on microsatellite markers. COI analysis showed a genetic differentiation within the A. ervi species, but the structure was neither associated with the commercial/wild status nor with host species factors. On the other hand, using microsatellite markers, we showed a genetic differentiation between commercial and wild A. ervi populations associated with a loss of genetic diversity within the mass-reared populations. Our ecological genetics study may potentially explain the weak efficiency of biological control of aphids in protected strawberry crops and enable to provide some insights to improve biological control.

RevDate: 2021-09-28
CmpDate: 2021-09-28

de Meeûs d'Argenteuil C, Boshuizen B, Oosterlinck M, et al (2021)

Flexibility of equine bioenergetics and muscle plasticity in response to different types of training: An integrative approach, questioning existing paradigms.

PloS one, 16(4):e0249922.

Equine bioenergetics have predominantly been studied focusing on glycogen and fatty acids. Combining omics with conventional techniques allows for an integrative approach to broadly explore and identify important biomolecules. Friesian horses were aquatrained (n = 5) or dry treadmill trained (n = 7) (8 weeks) and monitored for: evolution of muscle diameter in response to aquatraining and dry treadmill training, fiber type composition and fiber cross-sectional area of the M. pectoralis, M. vastus lateralis and M. semitendinosus and untargeted metabolomics of the M. pectoralis and M. vastus lateralis in response to dry treadmill training. Aquatraining was superior to dry treadmill training to increase muscle diameter in the hindquarters, with maximum effect after 4 weeks. After dry treadmill training, the M. pectoralis showed increased muscle diameter, more type I fibers, decreased fiber mean cross sectional area, and an upregulated oxidative metabolic profile: increased β-oxidation (key metabolites: decreased long chain fatty acids and increased long chain acylcarnitines), TCA activity (intermediates including succinyl-carnitine and 2-methylcitrate), amino acid metabolism (glutamine, aromatic amino acids, serine, urea cycle metabolites such as proline, arginine and ornithine) and xenobiotic metabolism (especially p-cresol glucuronide). The M. vastus lateralis expanded its fast twitch profile, with decreased muscle diameter, type I fibers and an upregulation of glycolytic and pentose phosphate pathway activity, and increased branched-chain and aromatic amino acid metabolism (cis-urocanate, carnosine, homocarnosine, tyrosine, tryptophan, p-cresol-glucuronide, serine, methionine, cysteine, proline and ornithine). Trained Friesians showed increased collagen and elastin turn-over. Results show that branched-chain amino acids, aromatic amino acids and microbiome-derived xenobiotics need further study in horses. They feed the TCA cycle at steps further downstream from acetyl CoA and most likely, they are oxidized in type IIA fibers, the predominant fiber type of the horse. These study results underline the importance of reviewing existing paradigms on equine bioenergetics.

RevDate: 2021-09-28
CmpDate: 2021-09-28

Ressaissi Y, Amills M, Noce A, et al (2021)

Characterizing the Mitochondrial Diversity of Arbi Goats from Tunisia.

Biochemical genetics, 59(5):1225-1232.

Arbi is one of the main local goat breeds in Tunisia, representing an important economic resource in arid and hot areas where cattle and sheep cannot thrive successfully. In the current work, we have characterized the mitochondrial diversity of 26 Arbi goats by partially sequencing the mitochondrial D-loop region. These sequences plus 10 retrieved from GenBank were analyzed with the DnaSP v.5.10.1, evidencing the existence of 12 different haplotypes. Nucleotide and haplotype diversities were 0.02 and 0.96. Moreover, median-joining network analysis showed that all D-loop sequences from Arbi goats correspond to haplogroup A and that in general they do not cluster with sequences from other goat breeds. The high diversity that has been observed in North African goats is compatible with the maritime diffusion of the Neolithic package 10,000-7000 YBP. Moreover, there are evidences that local Tunisian breeds have been extensively crossed with highly productive transboundary breeds in order to improve meat and milk yields. These uncontrolled crossing practices may lead to the loss of alleles that play key roles in the adaptation of Tunisian local breeds to a harsh environment.

RevDate: 2021-09-26

Deng J, Assandri G, Chauhan P, et al (2021)

Wolbachia-driven selective sweep in a range expanding insect species.

BMC ecology and evolution, 21(1):181.

BACKGROUND: Evolutionary processes can cause strong spatial genetic signatures, such as local loss of genetic diversity, or conflicting histories from mitochondrial versus nuclear markers. Investigating these genetic patterns is important, as they may reveal obscured processes and players. The maternally inherited bacterium Wolbachia is among the most widespread symbionts in insects. Wolbachia typically spreads within host species by conferring direct fitness benefits, and/or by manipulating its host reproduction to favour infected over uninfected females. Under sufficient selective advantage, the mitochondrial haplotype associated with the favoured maternally-inherited symbiotic strains will spread (i.e. hitchhike), resulting in low mitochondrial genetic variation across the host species range.

METHOD: The common bluetail damselfly (Ischnura elegans: van der Linden, 1820) has recently emerged as a model organism for genetics and genomic signatures of range expansion during climate change. Although there is accumulating data on the consequences of such expansion on the genetics of I. elegans, no study has screened for Wolbachia in the damselfly genus Ischnura. Here, we present the biogeographic variation in Wolbachia prevalence and penetrance across Europe and Japan (including samples from 17 populations), and from close relatives in the Mediterranean area (i.e. I. genei: Rambur, 1842; and I. saharensis: Aguesse, 1958).

RESULTS: Our data reveal (a) multiple Wolbachia-strains, (b) potential transfer of the symbiont through hybridization, (c) higher infection rates at higher latitudes, and (d) reduced mitochondrial diversity in the north-west populations, indicative of hitchhiking associated with the selective sweep of the most common strain. We found low mitochondrial haplotype diversity in the Wolbachia-infected north-western European populations (Sweden, Scotland, the Netherlands, Belgium, France and Italy) of I. elegans, and, conversely, higher mitochondrial diversity in populations with low penetrance of Wolbachia (Ukraine, Greece, Montenegro and Cyprus). The timing of the selective sweep associated with infected lineages was estimated between 20,000 and 44,000 years before present, which is consistent with the end of the last glacial period about 20,000 years.

CONCLUSIONS: Our findings provide an example of how endosymbiont infections can shape spatial variation in their host evolutionary genetics during postglacial expansion. These results also challenge population genetic studies that do not consider the prevalence of symbionts in many insects, which we show can impact geographic patterns of mitochondrial genetic diversity.

RevDate: 2021-09-21

O'Leary BM, Oh GGK, AH Millar (2022)

High-Throughput Oxygen Consumption Measurements in Leaf Tissue Using Oxygen Sensitive Fluorophores.

Methods in molecular biology (Clifton, N.J.), 2363:63-75.

Respiratory rate measurements are crucial assays to understand mitochondrial biochemistry as well as metabolic regulation within tissues. Several technologies currently exist that can measure plant respiratory oxygen consumption or carbon dioxide evolution rates over short durations by either isolated mitochondria or plant tissues. Here we describe recently developed alternative methods for measuring tissue oxygen consumption rates (OCRs) using systems reliant on oxygen sensitive fluorophores. The methods described have distinct experimental advantages: they can allow high-throughput and long-duration measurements; and they are particularly suited to investigating the metabolic regulation of respiration by comparing OCRs among treatments or genotypes.

RevDate: 2021-09-23
CmpDate: 2021-09-21

Hong Z, Liao X, Ye Y, et al (2021)

A complete mitochondrial genome for fragrant Chinese rosewood (Dalbergia odorifera, Fabaceae) with comparative analyses of genome structure and intergenomic sequence transfers.

BMC genomics, 22(1):672.

BACKGROUND: Dalbergia odorifera is an economically and culturally important species in the Fabaceae because of the high-quality lumber and traditional Chinese medicines made from this plant, however, overexploitation has increased the scarcity of D. odorifera. Given the rarity and the multiple uses of this species, it is important to expand the genomic resources for utilizing in applications such as tracking illegal logging, determining effective population size of wild stands, delineating pedigrees in marker assisted breeding programs, and resolving gene networks in functional genomics studies. Even the nuclear and chloroplast genomes have been published for D. odorifera, the complete mitochondrial genome has not been assembled or assessed for sequence transfer to other genomic compartments until now. Such work is essential in understanding structural and functional genome evolution in a lineage (Fabaceae) with frequent intergenomic sequence transfers.

RESULTS: We integrated Illumina short-reads and PacBio CLR long-reads to assemble and annotate the complete mitochondrial genome of D. odorifera. The mitochondrial genome was organized as a single circular structure of 435 Kb in length containing 33 protein coding genes, 4 rRNA and 17 tRNA genes. Nearly 4.0% (17,386 bp) of the genome was annotated as repetitive DNA. From the sequence transfer analysis, it was found that 114 Kb of DNA originating from the mitochondrial genome has been transferred to the nuclear genome, with most of the transfer events having taken place relatively recently. The high frequency of sequence transfers from the mitochondria to the nuclear genome was similar to that of sequence transfer from the chloroplast to the nuclear genome.

CONCLUSION: For the first-time, the complete mitochondrial genome of D. odorifera was assembled in this study, which will provide a baseline resource in understanding genomic evolution in the highly specious Fabaceae. In particular, the assessment of intergenomic sequence transfer suggests that transfers have been common and recent indicating a possible role in environmental adaptation as has been found in other lineages. The high turnover rate of genomic colinearly and large differences in mitochondrial genome size found in the comparative analyses herein providing evidence for the rapid evolution of mitochondrial genome structure compared to chloroplasts in Faboideae. While phylogenetic analyses using functional genes indicate that mitochondrial genes are very slowly evolving compared to chloroplast genes.

RevDate: 2021-09-21

Møller IM, Rasmusson AG, OV Aken (2021)

Plant Mitochondria - Past, present and future.

The Plant journal : for cell and molecular biology [Epub ahead of print].

The study of plant mitochondria started in earnest around 1950 with the first isolations of mitochondria from animal and plant tissues. The first 35 years were spent establishing the basic properties of plant mitochondria and plant respiration using biochemical and physiological approaches. A number of unique properties (compared to mammalian mitochondria) were observed: (i) The ability to oxidize malate, glycine and cytosolic NAD(P)H at high rates. (ii) The partial insensitivity to rotenone, which turned out to be due to the presence of a second NADH dehydrogenase on the inner surface of the inner mitochondrial membrane in addition to the classical complex I NADH dehydrogenase. (iii) The partial insensitivity to cyanide, which turned out to be due to an alternative oxidase, which is also located on the inner surface of the inner mitochondrial membrane, in addition to the classical complex IV, cytochrome oxidase. With the appearance of molecular biology methods around 1985, followed by genomics, further unique properties were discovered: (iv) Plant mitochondrial DNA (mtDNA) is 10-600 times larger than the mammalian mtDNA, yet it only contains ca 50% more genes. (v) Plant mtDNA has kept the standard genetic code, and it has a low divergence rate with respect to point mutations, but a high recombinatorial activity. (vi) Mitochondrial mRNA maturation includes a uniquely complex set of activities for processing, splicing and editing (at hundreds of sites). (vii) Recombination in mtDNA creates novel reading frames that can produce male sterility. (viii) A large proteome of 2000-3000 different proteins containing many unique proteins such as 200-300 pentatricopeptide repeat proteins. We describe the present and fairly detailed picture of the structure and function of plant mitochondria and how the unique properties make their metabolism more flexible allowing them to be involved in many diverse processes in the plant cell, such as photosynthesis, photorespiration, CAM and C4 metabolism, heat production, temperature control, stress resistance mechanisms, programmed cell death and genomic evolution. However, it is still a challenge to understand how the regulation of metabolism and mtDNA expression works at the cellular level and how retrograde signaling from the mitochondria coordinates all those processes.

RevDate: 2021-09-15

Mallo N, Ovciarikova J, Martins-Duarte ES, et al (2021)

Depletion of a Toxoplasma porin leads to defects in mitochondrial morphology and contacts with the ER.

Journal of cell science pii:272183 [Epub ahead of print].

The Voltage Dependent Anion channel (VDAC) is a ubiquitous channel in the outer membrane of the mitochondrion with multiple roles in protein, metabolite and small molecule transport. In mammalian cells, VDAC, as part of a larger complex including the inositol triphosphate receptor, has been shown to have a role in mediating contacts between the mitochondria and endoplasmic reticulum (ER). We identify VDAC of the pathogenic apicomplexan Toxoplasma gondii and demonstrate its importance for parasite growth. We show that VDAC is involved in protein import and metabolite transfer to mitochondria. Further, depletion of VDAC resulted in significant morphological changes of the mitochondrion and ER, suggesting a role in mediating contacts between these organelles in T. gondii.

RevDate: 2021-09-14

Oono J, Hatakeyama Y, Yabiku T, et al (2021)

Effects of growth temperature and nitrogen nutrition on expression of C3-C4 intermediate traits in Chenopodium album.

Journal of plant research [Epub ahead of print].

Proto-Kranz plants represent an initial phase in the evolution from C3 to C3-C4 intermediate to C4 plants. The ecological and adaptive aspects of C3-C4 plants would provide an important clue to understand the evolution of C3-C4 plants. We investigated whether growth temperature and nitrogen (N) nutrition influence the expression of C3-C4 traits in Chenopodium album (proto-Kranz) in comparison with Chenopodium quinoa (C3). Plants were grown during 5 weeks at 20 or 30 °C under standard or low N supply levels (referred to as 20SN, 20LN, 30SN, and 30LN). Net photosynthetic rate and leaf N content were higher in 20SN and 30SN plants than in 20LN and 30LN plants of C. album but did not differ among growth conditions in C. quinoa. The CO2 compensation point (Γ) of C. album was lowest in 30LN plants (36 µmol mol-1), highest in 20SN plants (51 µmol mol-1), and intermediate in 20LN and 30SN plants, whereas Γ of C. quinoa did not differ among the growth conditions (51-52 µmol mol-1). The anatomical structure of leaves was not considerably affected by growth conditions in either species. However, ultrastructural observations in C. album showed that the number of mitochondria per mesophyll or bundle sheath (BS) cell was lower in 20LN and 30LN plants than in 20SN and 30SN plants. Immunohistochemical observations revealed that lower accumulation level of P-protein of glycine decarboxylase (GDC-P) in mesophyll mitochondria than in BS mitochondria is the major factor causing the decrease in Γ values in C. album plants grown under low N supply and high temperature. These results suggest that high growth temperature and low N supply lead to the expression of C3-C4 traits (the reduction of Γ) in the proto-Kranz plants of C. album through the regulation of GDC-P expression.

RevDate: 2021-09-26

Li L, Conradson DM, Bharat V, et al (2021)

A mitochondrial membrane-bridging machinery mediates signal transduction of intramitochondrial oxidation.

Nature metabolism, 3(9):1242-1258.

Mitochondria are the main site for generating reactive oxygen species, which are key players in diverse biological processes. However, the molecular pathways of redox signal transduction from the matrix to the cytosol are poorly defined. Here we report an inside-out redox signal of mitochondria. Cysteine oxidation of MIC60, an inner mitochondrial membrane protein, triggers the formation of disulfide bonds and the physical association of MIC60 with Miro, an outer mitochondrial membrane protein. The oxidative structural change of this membrane-crossing complex ultimately elicits cellular responses that delay mitophagy, impair cellular respiration and cause oxidative stress. Blocking the MIC60-Miro interaction or reducing either protein, genetically or pharmacologically, extends lifespan and health-span of healthy fruit flies, and benefits multiple models of Parkinson's disease and Friedreich's ataxia. Our discovery provides a molecular basis for common treatment strategies against oxidative stress.

RevDate: 2021-09-11

Tůmová P, Voleman L, Klingl A, et al (2021)

Inheritance of the reduced mitochondria of Giardia intestinalis is coupled to the flagellar maturation cycle.

BMC biology, 19(1):193.

BACKGROUND: The presence of mitochondria is a distinguishing feature between prokaryotic and eukaryotic cells. It is currently accepted that the evolutionary origin of mitochondria coincided with the formation of eukaryotes and from that point control of mitochondrial inheritance was required. Yet, the way the mitochondrial presence has been maintained throughout the eukaryotic cell cycle remains a matter of study. Eukaryotes control mitochondrial inheritance mainly due to the presence of the genetic component; still only little is known about the segregation of mitochondria to daughter cells during cell division. Additionally, anaerobic eukaryotic microbes evolved a variety of genomeless mitochondria-related organelles (MROs), which could be theoretically assembled de novo, providing a distinct mechanistic basis for maintenance of stable mitochondrial numbers. Here, we approach this problem by studying the structure and inheritance of the protist Giardia intestinalis MROs known as mitosomes.

RESULTS: We combined 2D stimulated emission depletion (STED) microscopy and focused ion beam scanning electron microscopy (FIB/SEM) to show that mitosomes exhibit internal segmentation and conserved asymmetric structure. From a total of about forty mitosomes, a small, privileged population is harnessed to the flagellar apparatus, and their life cycle is coordinated with the maturation cycle of G. intestinalis flagella. The orchestration of mitosomal inheritance with the flagellar maturation cycle is mediated by a microtubular connecting fiber, which physically links the privileged mitosomes to both axonemes of the oldest flagella pair and guarantees faithful segregation of the mitosomes into the daughter cells.

CONCLUSION: Inheritance of privileged Giardia mitosomes is coupled to the flagellar maturation cycle. We propose that the flagellar system controls segregation of mitochondrial organelles also in other members of this supergroup (Metamonada) of eukaryotes and perhaps reflects the original strategy of early eukaryotic cells to maintain this key organelle before mitochondrial fusion-fission dynamics cycle as observed in Metazoa was established.

RevDate: 2021-09-08

Moroz LL, DY Romanova (2021)

Selective Advantages of Synapses in Evolution.

Frontiers in cell and developmental biology, 9:726563.

RevDate: 2021-09-05

Montes de Oca Balderas P (2021)

Mitochondria-plasma membrane interactions and communication.

The Journal of biological chemistry pii:S0021-9258(21)00966-2 [Epub ahead of print].

Mitochondria are known as the powerhouses of eukaryotic cells; however, they perform many other functions besides oxidative phosphorylation, including Ca2+ homeostasis, lipid metabolism, anti-viral response, and apoptosis. Although other hypotheses exist, mitochondria are generally thought as descendants of an α-proteobacteria that adapted to the intracellular environment within an Asgard archeobacteria, that have been studied for decades as an organelle subdued by the eukaryotic cell. Nevertheless, several early electron microscopy observations hinted that some mitochondria establish specific interactions with certain plasma membrane (PM) domains in mammalian cells. Furthermore, recent findings have documented the direct physical and functional interaction of mitochondria and the PM, the organization of distinct complexes, and their communication through vesicular means. In yeast, some molecular players mediating this interaction have been elucidated, but only a few works have studied this interaction in mammalian cells. In addition, mitochondria can be translocated among cells through tunneling nanotubes or by other mechanisms, and free, intact, functional mitochondria have been reported in the blood plasma. Together, these findings challenge the conception of mitochondria as organelles subdued by the eukaryotic cell. This review discusses the evidence of the mitochondria interaction with the PM that has been long disregarded, despite its importance in cell function, pathogenesis, and evolution. It also proposes a scheme of mitochondria-PM interactions with the intent to promote research and knowledge of this emerging pathway that promises to shift the current paradigms of cell biology.

RevDate: 2021-08-28

Mahapatra K, Banerjee S, De S, et al (2021)

An Insight Into the Mechanism of Plant Organelle Genome Maintenance and Implications of Organelle Genome in Crop Improvement: An Update.

Frontiers in cell and developmental biology, 9:671698.

Besides the nuclear genome, plants possess two small extra chromosomal genomes in mitochondria and chloroplast, respectively, which contribute a small fraction of the organelles' proteome. Both mitochondrial and chloroplast DNA have originated endosymbiotically and most of their prokaryotic genes were either lost or transferred to the nuclear genome through endosymbiotic gene transfer during the course of evolution. Due to their immobile nature, plant nuclear and organellar genomes face continuous threat from diverse exogenous agents as well as some reactive by-products or intermediates released from various endogenous metabolic pathways. These factors eventually affect the overall plant growth and development and finally productivity. The detailed mechanism of DNA damage response and repair following accumulation of various forms of DNA lesions, including single and double-strand breaks (SSBs and DSBs) have been well documented for the nuclear genome and now it has been extended to the organelles also. Recently, it has been shown that both mitochondria and chloroplast possess a counterpart of most of the nuclear DNA damage repair pathways and share remarkable similarities with different damage repair proteins present in the nucleus. Among various repair pathways, homologous recombination (HR) is crucial for the repair as well as the evolution of organellar genomes. Along with the repair pathways, various other factors, such as the MSH1 and WHIRLY family proteins, WHY1, WHY2, and WHY3 are also known to be involved in maintaining low mutation rates and structural integrity of mitochondrial and chloroplast genome. SOG1, the central regulator in DNA damage response in plants, has also been found to mediate endoreduplication and cell-cycle progression through chloroplast to nucleus retrograde signaling in response to chloroplast genome instability. Various proteins associated with the maintenance of genome stability are targeted to both nuclear and organellar compartments, establishing communication between organelles as well as organelles and nucleus. Therefore, understanding the mechanism of DNA damage repair and inter compartmental crosstalk mechanism in various sub-cellular organelles following induction of DNA damage and identification of key components of such signaling cascades may eventually be translated into strategies for crop improvement under abiotic and genotoxic stress conditions. This review mainly highlights the current understanding as well as the importance of different aspects of organelle genome maintenance mechanisms in higher plants.

RevDate: 2021-08-28

Rolland C, Andreani J, Sahmi-Bounsiar D, et al (2021)

Clandestinovirus: A Giant Virus With Chromatin Proteins and a Potential to Manipulate the Cell Cycle of Its Host Vermamoeba vermiformis.

Frontiers in microbiology, 12:715608.

For several decades, the vast world of DNA viruses has been expanding constantly. Various discoveries in this field have broadened our knowledge and revealed that DNA viruses encode many functional features, which were once thought to be exclusive to cellular life. Here, we report the isolation of a giant virus named "clandestinovirus," grown on the amoebal host Vermamoeba vermiformis. This virus was discovered in a mixed co-culture associated with another giant virus, Faustovirus ST1. Clandestinovirus possesses a linear dsDNA genome of 581,987 base pairs containing 617 genes. Phylogenetically, clandestinovirus is most closely related to Acanthamoeba castellanii medusavirus and was considered a member of the proposed Medusaviridae family. However, clandestinovirus genome is 65% larger than that of medusavirus, emphasizing the considerable genome size variation within this virus family. Functional annotation of the clandestinovirus genes suggests that the virus encodes four core histones. Furthermore, clandestinovirus appears to orchestrate the cell cycle and mitochondrial activities of the infected host by virtue of encoding a panel of protein kinases and phosphatases, and a suite of functionally diverse mitochondrial protein homologs, respectively. Collectively, these observations illuminate a strategy employed by clandestinovirus to optimize the intracellular environment for efficient virus propagation.

RevDate: 2021-09-16

Satoh T (2021)

Bird evolution by insulin resistance.

Trends in endocrinology and metabolism: TEM, 32(10):803-813.

Drift of oxygen concentrations in the atmosphere was one of the main drivers of the evolution of vertebrates. The drop in oxygen concentrations at the Permian-Triassic (PT) boundary may have been the biggest challenge to vertebrates. This hypoxic condition forced theropods to lose certain genes to maximize their efficiency of oxygen usage. Recent studies show that omentin and insulin-sensitive glucose transporter 4 (GLUT4) are missing in the bird genome. Since these gene products play essential roles in maintaining insulin sensitivity, this loss forced theropods to become insulin resistant. Insulin resistance may have been the key to allowing theropods to become hyperathletic under hypoxic conditions and to outcompete mammals during the Triassic period. A second challenge was the gradual increase in oxygen concentrations during the late Jurassic, Cretaceous, and Tertiary periods when reactive oxygen species (ROS) leakage from mitochondria became a problem. Since the simplest solution was the expansion of body size, some theropods became bigger to reduce ROS leakage per volume. Another solution was the development of a constitutively active countermeasure against ROS. A recent study shows that Neoaves have constitutively active nuclear factor erythroid 2-related factor 2 (NRF2) due to deletion of the C-terminal part of the KEAP1 protein, thus allowing Neoaves to express antioxidant enzymes to overcome ROS leakage.

RevDate: 2021-08-31

Kwak Y (2021)

An Update on Trichoderma Mitogenomes: Complete De Novo Mitochondrial Genome of the Fungal Biocontrol Agent Trichoderma harzianum (Hypocreales, Sordariomycetes), an Ex-Neotype Strain CBS 226.95, and Tracing the Evolutionary Divergences of Mitogenomes in Trichoderma.

Microorganisms, 9(8):.

Members of the genus Trichoderma (Hypocreales), widely used as biofungicides, biofertilizers, and as model fungi for the industrial production of CAZymes, have actively been studied for the applications of their biological functions. Recently, the study of the nuclear genomes of Trichoderma has expanded in the directions of adaptation and evolution to gain a better understanding of their ecological traits. However, Trichoderma's mitochondria have received much less attention despite mitochondria being the most necessary element for sustaining cell life. In this study, a mitogenome of the fungus Trichoderma harzianum CBS 226.95 was assembled de novo. A 27,632 bp circular DNA molecule was revealed with specific features, such as the intronless of all core PCGs, one homing endonuclease, and a putative overlapping tRNA, on a closer phylogenetic relationship with T. reesei among hypocrealean fungi. Interestingly, the mitogenome of T. harzianum CBS 226.95 was predicted to have evolved earlier than those of other Trichoderma species and also assumed with a selection pressure in the cox3. Considering the bioavailability, both for the ex-neotype strain of the T. harzianum species complex and the most globally representative commercial fungal biocontrol agent, our results on the T. harzianum CBS 226.95 mitogenome provide crucial information which will be helpful criteria in future studies on Trichoderma.

RevDate: 2021-08-30

Stewart DT, Robicheau BM, Youssef N, et al (2021)

Expanding the Search for Sperm Transmission Elements in the Mitochondrial Genomes of Bivalve Mollusks.

Genes, 12(8):.

Doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA) in bivalve mollusks is one of the most notable departures from the paradigm of strict maternal inheritance of mtDNA among metazoans. Recently, work on the Mediterranean mussel Mytilus galloprovincialis suggested that a nucleotide motif in the control region of this species, known as the sperm transmission element (STE), helps protect male-transmitted mitochondria from destruction during spermatogenesis. Subsequent studies found similar, yet divergent, STE motifs in other marine mussels. Here, we extend the in silico search for mtDNA signatures resembling known STEs. This search is carried out for the large unassigned regions of 157 complete mitochondrial genomes from within the Mytiloida, Veneroida, Unionoida, and Ostreoida bivalve orders. Based on a sliding window approach, we present evidence that there are additional putative STE signatures in the large unassigned regions of several marine clams and freshwater mussels with DUI. We discuss the implications of this finding for interpreting the origin of doubly uniparental inheritance in ancestral bivalve mollusks, as well as potential future in vitro and in silico studies that could further refine our understanding of the early evolution of this unusual system of mtDNA inheritance.

RevDate: 2021-08-26

Petrů M, Dohnálek V, Füssy Z, et al (2021)

Fates of Sec, Tat and YidC translocases in mitochondria and other eukaryotic compartments.

Molecular biology and evolution pii:6358141 [Epub ahead of print].

Formation of mitochondria by the conversion of a bacterial endosymbiont was a key moment in the evolution of eukaryotes. It was made possible by outsourcing the endosymbiont's genetic control to the host nucleus, while developing the import machinery for proteins synthesized on cytosolic ribosomes. The original protein export machines of the nascent organelle remained to be re-purposed or were completely abandoned. This review follows the evolutionary fates of three prokaryotic inner membrane translocases Sec, Tat and YidC. Homologues of all three translocases can still be found in current mitochondria, but with different importance for mitochondrial function. While the mitochondrial YidC homologue, Oxa1, became an omnipresent independent insertase, the other two remained only sporadically present in mitochondria. Only a single substrate is known for the mitochondrial Tat and no function has yet been assigned for the mitochondrial Sec. Finally, this review compares these ancestral mitochondrial proteins with their paralogues operating in the plastids and the endomembrane system.

RevDate: 2021-08-24

Cooper LN (2021)

Metabolism: Evolution of dolphin sperm endurance.

Current biology : CB, 31(16):R1006-R1008.

Mammalian sperm have long been known to use energy derived from the metabolism of sugars and fatty acids. A new study shows that sperm of dolphins and their relatives lost functionality of the glycolysis pathway and are fueled only by energy-rich fatty acids that are metabolized by extra-large mitochondria, giving them exceptional endurance.

RevDate: 2021-09-26

Lyra GM, Iha C, Grassa CJ, et al (2021)

Phylogenomics, divergence time estimation and trait evolution provide a new look into the Gracilariales (Rhodophyta).

Molecular phylogenetics and evolution, 165:107294 pii:S1055-7903(21)00227-X [Epub ahead of print].

The Gracilariales is a highly diverse, widely distributed order of red algae (Rhodophyta) that forms a well-supported clade. Aside from their ecological importance, species of Gracilariales provide important sources of agarans and possess bioactive compounds with medicinal and pharmaceutical use. Recent phylogenetic analyses from a small number of genes have greatly advanced our knowledge of evolutionary relationships in this clade, yet several key nodes were not especially well resolved. We assembled a phylogenomic data set containing 79 nuclear genes, 195 plastid genes, and 24 mitochondrial genes from species representing all three major Gracilariales lineages, including: Melanthalia, Gracilariopsis, and Gracilaria sensu lato. This data set leads to a fully-resolved phylogeny of Gracilariales, which is highly-consistent across genomic compartments. In agreement with previous findings, Melanthalia obtusata was sister to a clade including Gracilaria s.l. and Gracilariopsis, which were each resolved as well-supported clades. Our results also clarified the long-standing uncertainty about relationships in Gracilaria s.l., not resolved in single and multi-genes approaches. We further characterized the divergence time, organellar genome architecture, and morphological trait evolution in Gracilarales to better facilitate its taxonomic treatment. Gracilariopsis and Gracilaria s.l. are comparable taxonomic ranks, based on the overlapping time range of their divergence. The genomic structure of plastid and mitochondria is highly conserved within each clade but differs slightly among these clades in gene contents. For example, the plastid gene petP is lost in Gracilaria s.l. and the mitochondrial gene trnH is in different positions in the genome of Gracilariopsis and Gracilaria s.l. Our analyses of ancestral character evolution provide evidence that the main characters used to delimitate genera in Gracilariales, such as spermatangia type and features of the cystocarp's anatomy, overlap in subclades of Gracilaria s.l. We discuss the taxonomy of Gracilariales in light of these results and propose an objective and practical classification, which is in agreement with the criteria of monophyly, exclusive characters, predictability and nomenclatural stability.

RevDate: 2021-09-03

Jakovlić I, Zou H, Chen JH, et al (2021)

Slow crabs - fast genomes: Locomotory capacity predicts skew magnitude in crustacean mitogenomes.

Molecular ecology [Epub ahead of print].

Base composition skews (G-C/G+C) of mitochondrial genomes are believed to be primarily driven by mutational pressure, which is positively correlated with metabolic rate. In marine animals, metabolic rate is also positively correlated with locomotory capacity. Given the central role of mitochondria in energy metabolism, we hypothesised that selection for locomotory capacity should be positively correlated with the strength of purifying selection (dN/dS), and thus be negatively correlated with the skew magnitude. Therefore, these two models assume diametrically opposite associations between the metabolic rate and skew magnitude: positive correlation in the prevailing paradigm, and negative in our working hypothesis. We examined correlations between the skew magnitude, metabolic rate, locomotory capacity, and several other variables previously associated with mitochondrial evolution on 287 crustacean mitogenomes. Weakly locomotory taxa had higher skew magnitude and ω (dN/dS) values, but not the gene order rearrangement rate. Skew and ω magnitudes were correlated. Multilevel regression analyses indicated that three competing variables, body size, gene order rearrangement rate, and effective population size, had negligible impacts on the skew magnitude. In most crustacean lineages selection for locomotory capacity appears to be the primary factor determining the skew magnitude. Contrary to the prevailing paradigm, this implies that adaptive selection outweighs nonadaptive selection (mutation pressure) in crustaceans. However, we found indications that effective population size (nonadaptive factor) may outweigh the impact of locomotory capacity in sessile crustaceans (Thecostraca). In conclusion, skew magnitude is a product of the interplay between adaptive and nonadaptive factors, the balance of which varies among lineages.

RevDate: 2021-08-29

Jenkins EC, O'Connell MJ, Manfredi G, et al (2021)

Doxycycline promotes proteasome fitness in the central nervous system.

Scientific reports, 11(1):17003.

Several studies reported that mitochondrial stress induces cytosolic proteostasis in yeast and C. elegans. Notably, inhibition of mitochondrial translation with doxcycyline decreases the toxicity of β-amyloid aggregates, in a C. elegans. However, how mitochondrial stress activates cytosolic proteostasis remains unclear. Further whether doxycycline has this effect in mammals and in disease relevant tissues also remains unclear. We show here that doxycycline treatment in mice drastically reduces the accumulation of proteins destined for degradation by the proteasome in a CNS region-specific manner. This effect is associated with the activation of the ERα axis of the mitochondrial unfolded protein response (UPRmt), in both males and females. However, sexually dimorphic mechanisms of proteasome activation were observed. Doxycycline also activates the proteasome in fission yeast, where ERα is not expressed. Rather, the ancient ERα-coactivator Mms19 regulates this response in yeast. Our results suggest that the UPRmt initiates a conserved mitochondria-to-cytosol stress signal, resulting in proteasome activation, and that this signal has adapted during evolution, in a sex and tissue specific-manner. Therefore, while our results support the use of doxycycline in the prevention of proteopathic diseases, they also indicate that sex is an important variable to consider in the design of future clinical trials using doxycycline.

RevDate: 2021-09-02

Karia P, Yoshioka K, W Moeder (2021)

Multiple phosphorylation events of the mitochondrial membrane protein TTM1 regulate cell death during senescence.

The Plant journal : for cell and molecular biology [Epub ahead of print].

The role of mitochondria in programmed cell death (PCD) during animal growth and development is well documented, but much less is known for plants. We previously showed that the Arabidopsis thaliana triphosphate tunnel metalloenzyme (TTM) proteins TTM1 and TTM2 are tail-anchored proteins that localize in the mitochondrial outer membrane and participate in PCD during senescence and immunity, respectively. Here, we show that TTM1 is specifically involved in senescence induced by abscisic acid (ABA). Moreover, phosphorylation of TTM1 by multiple mitogen-activated protein (MAP) kinases regulates its function and turnover. A combination of proteomics and in vitro kinase assays revealed three major phosphorylation sites of TTM1 (Ser10, Ser437, and Ser490). Ser437, which is phosphorylated upon perception of senescence cues such as ABA and prolonged darkness, is phosphorylated by the MAP kinases MPK3 and MPK4, and Ser437 phosphorylation is essential for TTM1 function in senescence. These MPKs, together with three additional MAP kinases (MPK1, MPK7, and MPK6), also phosphorylate Ser10 and Ser490, marking TTM1 for protein turnover, which likely prevents uncontrolled cell death. Taken together, our results show that multiple MPKs regulate the function and turnover of the mitochondrial protein TTM1 during senescence-associated cell death, revealing a novel link between mitochondria and PCD.

RevDate: 2021-08-25

Bettinazzi S, Milani L, Blier PU, et al (2021)

Bioenergetic consequences of sex-specific mitochondrial DNA evolution.

Proceedings. Biological sciences, 288(1957):20211585.

Doubly uniparental inheritance (DUI) represents a notable exception to the general rule of strict maternal inheritance (SMI) of mitochondria in metazoans. This system entails the coexistence of two mitochondrial lineages (F- and M-type) transmitted separately through oocytes and sperm, thence providing an unprecedented opportunity for the mitochondrial genome to evolve adaptively for male functions. In this study, we explored the impact of a sex-specific mitochondrial evolution upon gamete bioenergetics of DUI and SMI bivalve species, comparing the activity of key enzymes of glycolysis, fermentation, fatty acid metabolism, tricarboxylic acid cycle, oxidative phosphorylation and antioxidant metabolism. Our findings suggest reorganized bioenergetic pathways in DUI gametes compared to SMI gametes. This generally results in a decreased enzymatic capacity in DUI sperm with respect to DUI oocytes, a limitation especially prominent at the terminus of the electron transport system. This bioenergetic remodelling fits a reproductive strategy that does not require high energy input and could potentially link with the preservation of the paternally transmitted mitochondrial genome in DUI species. Whether this phenotype may derive from positive or relaxed selection acting on DUI sperm is still uncertain.

RevDate: 2021-09-16

Muthye V, DV Lavrov (2021)

Multiple Losses of MSH1, Gain of mtMutS, and Other Changes in the MutS Family of DNA Repair Proteins in Animals.

Genome biology and evolution, 13(9):.

MutS is a key component of the mismatch repair (MMR) pathway. Members of the MutS protein family are present in prokaryotes, eukaryotes, and viruses. Six MutS homologs (MSH1-6) have been identified in yeast, of which three function in nuclear MMR, while MSH1 functions in mitochondrial DNA repair. MSH proteins are believed to be well conserved in animals, except for MSH1-which is thought to be lost. Two intriguing exceptions to this general picture have been found, both in the class Anthozoa within the phylum Cnidaria. First, an ortholog of the yeast-MSH1 was reported in one hexacoral species. Second, a MutS homolog (mtMutS) has been found in the mitochondrial genome of all octocorals. To understand the origin and potential functional implications of these exceptions, we investigated the evolution of the MutS family both in Cnidaria and in animals in general. Our study confirmed the acquisition of octocoral mtMutS by horizontal gene transfer from a giant virus. Surprisingly, we identified MSH1 in all hexacorals and several sponges and placozoans. By contrast, MSH1 orthologs were lacking in other cnidarians, ctenophores, and bilaterian animals. Furthermore, while we identified MSH2 and MSH6 in nearly all animals, MSH4, MSH5, and, especially, MSH3 were missing in multiple species. Overall, our analysis revealed a dynamic evolution of the MutS family in animals, with multiple losses of MSH1, MSH3, some losses of MSH4 and MSH5, and a gain of the octocoral mtMutS. We propose that octocoral mtMutS functionally replaced MSH1 that was present in the common ancestor of Anthozoa.

RevDate: 2021-09-08

Kowalczyk A, Gbadamosi O, Kolor K, et al (2021)

Evolutionary rate covariation identifies SLC30A9 (ZnT9) as a mitochondrial zinc transporter.

The Biochemical journal, 478(17):3205-3220.

Recent advances in genome sequencing have led to the identification of new ion and metabolite transporters, many of which have not been characterized. Due to the variety of subcellular localizations, cargo and transport mechanisms, such characterization is a daunting task, and predictive approaches focused on the functional context of transporters are very much needed. Here we present a case for identifying a transporter localization using evolutionary rate covariation (ERC), a computational approach based on pairwise correlations of amino acid sequence evolutionary rates across the mammalian phylogeny. As a case study, we find that poorly characterized transporter SLC30A9 (ZnT9) coevolves with several components of the mitochondrial oxidative phosphorylation chain, suggesting mitochondrial localization. We confirmed this computational finding experimentally using recombinant human SLC30A9. SLC30A9 loss caused zinc mishandling in the mitochondria, suggesting that under normal conditions it acts as a zinc exporter. We therefore propose that ERC can be used to predict the functional context of novel transporters and other poorly characterized proteins.

RevDate: 2021-09-08

Calderon RH, Å Strand (2021)

How retrograde signaling is intertwined with the evolution of photosynthetic eukaryotes.

Current opinion in plant biology, 63:102093 pii:S1369-5266(21)00093-5 [Epub ahead of print].

Chloroplasts and mitochondria evolved from free-living prokaryotic organisms that entered the eukaryotic cell through endosymbiosis. The gradual conversion from endosymbiont to organelle during the course of evolution was accompanied by the development of a communication system between the host and the endosymbiont, referred to as retrograde signaling or organelle-to-nucleus signaling. In higher plants, plastid-to-nucleus signaling involves multiple signaling pathways necessary to coordinate plastid function and cellular responses to developmental and environmental stimuli. Phylogenetic reconstructions using sequence information from evolutionarily diverse photosynthetic eukaryotes have begun to provide information about how retrograde signaling pathways were adopted and modified in different lineages over time. A tight communication system was likely a major facilitator of plants conquest of the land because it would have enabled the algal ancestors of land plants to better allocate their cellular resources in response to high light and desiccation, the major stressor for streptophyte algae in a terrestrial habitat. In this review, we aim to give an evolutionary perspective on plastid-to-nucleus signaling.

RevDate: 2021-08-18
CmpDate: 2021-08-17

Morrow JL, M Riegler (2021)

Genome analyses of four Wolbachia strains and associated mitochondria of Rhagoletis cerasi expose cumulative modularity of cytoplasmic incompatibility factors and cytoplasmic hitchhiking across host populations.

BMC genomics, 22(1):616.

BACKGROUND: The endosymbiont Wolbachia can manipulate arthropod reproduction and invade host populations by inducing cytoplasmic incompatibility (CI). Some host species are coinfected with multiple Wolbachia strains which may have sequentially invaded host populations by expressing different types of modular CI factor (cif) genes. The tephritid fruit fly Rhagoletis cerasi is a model for CI and Wolbachia population dynamics. It is associated with at least four Wolbachia strains in various combinations, with demonstrated (wCer2, wCer4), predicted (wCer1) or unknown (wCer5) CI phenotypes.

RESULTS: We sequenced and assembled the draft genomes of the Wolbachia strains wCer1, wCer4 and wCer5, and compared these with the previously sequenced genome of wCer2 which currently invades R. cerasi populations. We found complete cif gene pairs in all strains: four pairs in wCer2 (three Type I; one Type V), two pairs in wCer1 (both Type I) and wCer4 (one Type I; one Type V), and one pair in wCer5 (Type IV). Wolbachia genome variant analyses across geographically and genetically distant host populations revealed the largest diversity of single nucleotide polymorphisms (SNPs) in wCer5, followed by wCer1 and then wCer2, indicative of their different lengths of host associations. Furthermore, mitogenome analyses of the Wolbachia genome-sequenced individuals in combination with SNP data from six European countries revealed polymorphic mitogenome sites that displayed reduced diversity in individuals infected with wCer2 compared to those without.

CONCLUSIONS: Coinfections with Wolbachia are common in arthropods and affect options for Wolbachia-based management strategies of pest and vector species already infected by Wolbachia. Our analyses of Wolbachia genomes of a host naturally coinfected by several strains unravelled signatures of the evolutionary dynamics in both Wolbachia and host mitochondrial genomes as a consequence of repeated invasions. Invasion of already infected populations by new Wolbachia strains requires new sets of functionally different cif genes and thereby may select for a cumulative modularity of cif gene diversity in invading strains. Furthermore, we demonstrated at the mitogenomic scale that repeated CI-driven Wolbachia invasions of hosts result in reduced mitochondrial diversity and hitchhiking effects. Already resident Wolbachia strains may experience similar cytoplasmic hitchhiking effects caused by the invading Wolbachia strain.

RevDate: 2021-08-13

Scott GR, AC Dalziel (2021)

Physiological insight into the evolution of complex phenotypes: aerobic performance and the O2 transport pathway of vertebrates.

The Journal of experimental biology, 224(16):.

Evolutionary physiology strives to understand how the function and integration of physiological systems influence the way in which organisms evolve. Studies of the O2 transport pathway - the integrated physiological system that transports O2 from the environment to mitochondria - are well suited to this endeavour. We consider the mechanistic underpinnings across the O2 pathway for the evolution of aerobic capacity, focusing on studies of artificial selection and naturally selected divergence among wild populations of mammals and fish. We show that evolved changes in aerobic capacity do not require concerted changes across the O2 pathway and can arise quickly from changes in one or a subset of pathway steps. Population divergence in aerobic capacity can be associated with the evolution of plasticity in response to environmental variation or activity. In some cases, initial evolutionary divergence of aerobic capacity arose exclusively from increased capacities for O2 diffusion and/or utilization in active O2-consuming tissues (muscle), which may often constitute first steps in adaptation. However, continued selection leading to greater divergence in aerobic capacity is often associated with increased capacities for circulatory and pulmonary O2 transport. Increases in tissue O2 diffusing capacity may augment the adaptive benefit of increasing circulatory O2 transport owing to their interactive influence on tissue O2 extraction. Theoretical modelling of the O2 pathway suggests that O2 pathway steps with a disproportionately large influence over aerobic capacity have been more likely to evolve, but more work is needed to appreciate the extent to which such physiological principles can predict evolutionary outcomes.

RevDate: 2021-09-26

Aboouf MA, Armbruster J, Thiersch M, et al (2021)

Myoglobin, expressed in brown adipose tissue of mice, regulates the content and activity of mitochondria and lipid droplets.

Biochimica et biophysica acta. Molecular and cell biology of lipids, 1866(12):159026.

The identification of novel physiological regulators that stimulate energy expenditure through brown adipose tissue (BAT) activity in substrate catalysis is of utmost importance to understand and treat metabolic diseases. Myoglobin (MB), known to store or transport oxygen in heart and skeletal muscles, has recently been found to bind fatty acids with physiological constants in its oxygenated form (i.e., MBO2). Here, we investigated the in vivo effect of MB expression on BAT activity. In particular, we studied mitochondrial function and lipid metabolism as essential determinants of energy expenditure in this tissue. We show in a MB-null (MBko) mouse model that MB expression in BAT impacts on the activity of brown adipocytes in a twofold manner: i) by elevating mitochondrial density plus maximal respiration capacity, and through that, by stimulating BAT oxidative metabolism along with the organelles` uncoupled respiration; and ii) by influencing the free fatty acids pool towards a palmitate-enriched composition and shifting the lipid droplet (LD) equilibrium towards higher counts of smaller droplets. These metabolic changes were accompanied by the up-regulated expression of thermogenesis markers UCP1, CIDEA, CIDEC, PGC1-α and PPAR-α in the BAT of MB wildtype (MBwt) mice. Along with the emergence of the "browning" BAT morphology, MBwt mice exhibited a leaner phenotype when compared to MBko littermates at 20 weeks of age. Our data shed novel insights into MB's role in linking oxygen and lipid-based thermogenic metabolism. The findings suggest potential new strategies of targeting the MB pathway to treat metabolic disorders related to diminishing energy expenditure.

RevDate: 2021-08-17
CmpDate: 2021-08-16

Schäffer AA, McVeigh R, Robbertse B, et al (2021)

Ribovore: ribosomal RNA sequence analysis for GenBank submissions and database curation.

BMC bioinformatics, 22(1):400.

BACKGROUND: The DNA sequences encoding ribosomal RNA genes (rRNAs) are commonly used as markers to identify species, including in metagenomics samples that may combine many organismal communities. The 16S small subunit ribosomal RNA (SSU rRNA) gene is typically used to identify bacterial and archaeal species. The nuclear 18S SSU rRNA gene, and 28S large subunit (LSU) rRNA gene have been used as DNA barcodes and for phylogenetic studies in different eukaryote taxonomic groups. Because of their popularity, the National Center for Biotechnology Information (NCBI) receives a disproportionate number of rRNA sequence submissions and BLAST queries. These sequences vary in quality, length, origin (nuclear, mitochondria, plastid), and organism source and can represent any region of the ribosomal cistron.

RESULTS: To improve the timely verification of quality, origin and loci boundaries, we developed Ribovore, a software package for sequence analysis of rRNA sequences. The ribotyper and ribosensor programs are used to validate incoming sequences of bacterial and archaeal SSU rRNA. The ribodbmaker program is used to create high-quality datasets of rRNAs from different taxonomic groups. Key algorithmic steps include comparing candidate sequences against rRNA sequence profile hidden Markov models (HMMs) and covariance models of rRNA sequence and secondary-structure conservation, as well as other tests. Nine freely available blastn rRNA databases created and maintained with Ribovore are used for checking incoming GenBank submissions and used by the blastn browser interface at NCBI. Since 2018, Ribovore has been used to analyze more than 50 million prokaryotic SSU rRNA sequences submitted to GenBank, and to select at least 10,435 fungal rRNA RefSeq records from type material of 8350 taxa.

CONCLUSION: Ribovore combines single-sequence and profile-based methods to improve GenBank processing and analysis of rRNA sequences. It is a standalone, portable, and extensible software package for the alignment, classification and validation of rRNA sequences. Researchers planning on submitting SSU rRNA sequences to GenBank are encouraged to download and use Ribovore to analyze their sequences prior to submission to determine which sequences are likely to be automatically accepted into GenBank.

RevDate: 2021-08-09

Cooper ID, Brookler KH, Kyriakidou Y, et al (2021)

Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm.

Biomedicines, 9(7):.

Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin's primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.

RevDate: 2021-08-09

Prieto-Carrasco R, Silva-Palacios A, Rojas-Morales P, et al (2021)

Unilateral Ureteral Obstruction for 28 Days in Rats Is Not Associated with Changes in Cardiac Function or Alterations in Mitochondrial Function.

Biology, 10(7):.

Our work evaluated cardiac function and mitochondrial bioenergetics parameters in hearts from male Wistar rats subjected to the UUO model during 28 days of progression. We measured markers of kidney damage and inflammation in plasma and renal fibrosis by histological analysis and Western blot. Cardiac function was evaluated by echocardiography and proteins involved in cardiac damage by Western blot. Oxygen consumption and transmembrane potential were monitored in cardiac mitochondria using high-resolution respirometry. We also determined the activity of ATP synthase and antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase. Our results show that, although renal dysfunction is established in animals subjected to ureteral obstruction, cardiac function is maintained along with mitochondrial function and antioxidant enzymes activity after 28 days of injury evolution. Our results suggest that renocardiac syndrome might develop but belatedly in obstruction-induced renal damage, opening the opportunity for treatment to prevent this condition.

RevDate: 2021-08-03

Gabaldón T (2021)

Origin and Early Evolution of the Eukaryotic Cell.

Annual review of microbiology [Epub ahead of print].

The origin of eukaryotes has been defined as the major evolutionary transition since the origin of life itself. Most hallmark traits of eukaryotes, such as their intricate intracellular organization, can be traced back to a putative common ancestor that predated the broad diversity of extant eukaryotes. However, little is known about the nature and relative order of events that occurred in the path from preexisting prokaryotes to this already sophisticated ancestor. The origin of mitochondria from the endosymbiosis of an alphaproteobacterium is one of the few robustly established events to which most hypotheses on the origin of eukaryotes are anchored, but the debate is still open regarding the time of this acquisition, the nature of the host, and the ecological and metabolic interactions between the symbiotic partners. After the acquisition of mitochondria, eukaryotes underwent a fast radiation into several major clades whose phylogenetic relationships have been largely elusive. Recent progress in the comparative analyses of a growing number of genomes is shedding light on the early events of eukaryotic evolution as well as on the root and branching patterns of the tree of eukaryotes. Here I discuss current knowledge and debates on the origin and early evolution of eukaryotes. I focus particularly on how phylogenomic analyses have challenged some of the early assumptions about eukaryotic evolution, including the widespread idea that mitochondrial symbiosis in an archaeal host was the earliest event in eukaryogenesis. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see for revised estimates.

RevDate: 2021-09-20
CmpDate: 2021-09-20

Zhang Q, Wang Z, Zhang W, et al (2021)

The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels.

Nature cell biology, 23(8):870-880.

The memory of stresses experienced by parents can be passed on to descendants as a forecast of the challenges to come. Here, we discovered that the neuronal mitochondrial perturbation-induced systemic mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans can be transmitted to offspring over multiple generations. The transgenerational activation of UPRmt is mediated by maternal inheritance of elevated levels of mitochondrial DNA (mtDNA), which causes the proteostasis stress within mitochondria. Furthermore, results from intercrossing studies using wild C. elegans strains further support that maternal inheritance of higher levels of mtDNA can induce the UPRmt in descendants. The mitokine Wnt signalling pathway is required for the transmission of elevated mtDNA levels across generations, thereby conferring lifespan extension and stress resistance to offspring. Collectively, our results reveal that the nervous system can transmit stress signals across generations by increasing mtDNA in the germline, enabling descendants to better cope with anticipated challenges.

RevDate: 2021-08-08

Fernandes Gyorfy M, Miller ER, Conover JL, et al (2021)

Nuclear-cytoplasmic balance: whole genome duplications induce elevated organellar genome copy number.

The Plant journal : for cell and molecular biology [Epub ahead of print].

The plant genome is partitioned across three distinct subcellular compartments: the nucleus, mitochondria, and plastids. Successful coordination of gene expression among these organellar genomes and the nuclear genome is critical for plant function and fitness. Whole genome duplication (WGD) events in the nucleus have played a major role in the diversification of land plants and are expected to perturb the relative copy number (stoichiometry) of nuclear, mitochondrial, and plastid genomes. Thus, elucidating the mechanisms whereby plant cells respond to the cytonuclear stoichiometric imbalance that follows WGDs represents an important yet underexplored question in understanding the evolutionary consequences of genome doubling. We used droplet digital PCR to investigate the relationship between nuclear and organellar genome copy numbers in allopolyploids and their diploid progenitors in both wheat and Arabidopsis. Polyploids exhibit elevated organellar genome copy numbers per cell, largely preserving the cytonuclear stoichiometry observed in diploids despite the change in nuclear genome copy number. To investigate the timescale over which cytonuclear stoichiometry may respond to WGD, we also estimated the organellar genome copy number in Arabidopsis synthetic autopolyploids and in a haploid-induced diploid line. We observed corresponding changes in organellar genome copy number in these laboratory-generated lines, indicating that at least some of the cellular response to cytonuclear stoichiometric imbalance is immediate following WGD. We conclude that increases in organellar genome copy numbers represent a common response to polyploidization, suggesting that maintenance of cytonuclear stoichiometry is an important component in establishing polyploid lineages.

RevDate: 2021-09-10

Colnaghi M, Pomiankowski A, N Lane (2021)

The need for high-quality oocyte mitochondria at extreme ploidy dictates mammalian germline development.

eLife, 10:.

Selection against deleterious mitochondrial mutations is facilitated by germline processes, lowering the risk of genetic diseases. How selection works is disputed: experimental data are conflicting and previous modeling work has not clarified the issues; here, we develop computational and evolutionary models that compare the outcome of selection at the level of individuals, cells and mitochondria. Using realistic de novo mutation rates and germline development parameters from mouse and humans, the evolutionary model predicts the observed prevalence of mitochondrial mutations and diseases in human populations. We show the importance of organelle-level selection, seen in the selective pooling of mitochondria into the Balbiani body, in achieving high-quality mitochondria at extreme ploidy in mature oocytes. Alternative mechanisms debated in the literature, bottlenecks and follicular atresia, are unlikely to account for the clinical data, because neither process effectively eliminates mitochondrial mutations under realistic conditions. Our findings explain the major features of female germline architecture, notably the longstanding paradox of over-proliferation of primordial germ cells followed by massive loss. The near-universality of these processes across animal taxa makes sense in light of the need to maintain mitochondrial quality at extreme ploidy in mature oocytes, in the absence of sex and recombination.

RevDate: 2021-07-20

Xu X, Ma A, Li T, et al (2021)

Genetic and Functional Characterization of Novel Brown-Like Adipocytes Around the Lamprey Brain.

Frontiers in cell and developmental biology, 9:674939.

During the process of vertebrate evolution, many thermogenic organs and mechanisms have appeared. Mammalian brown adipose tissue (BAT) generates heat through the uncoupling oxidative phosphorylation of mitochondria, acts as a natural defense against hypothermia and inhibits the development of obesity. Although the existence, cellular origin and molecular identity of BAT in humans have been well studied, the genetic and functional characteristics of BAT from lampreys remain unknown. Here, we identified and characterized a novel, naturally existing brown-like adipocytes at the lamprey brain periphery. Similar to human BAT, the lamprey brain periphery contains brown-like adipocytes that maintain the same morphology as human brown adipocytes, containing multilocular lipid droplets and high mitochondrion numbers. Furthermore, we found that brown-like adipocytes in the periphery of lamprey brains responded to thermogenic reagent treatment and cold exposure and that lamprey UCP2 promoted precursor adipocyte differentiation. Molecular mapping by RNA-sequencing showed that inflammation in brown-like adipocytes treated with LPS and 25HC was enhanced compared to controls. The results of this study provide new evidence for human BAT research and demonstrate the multilocular adipose cell functions of lampreys, including: (1) providing material energy and protecting structure, (2) generating additional heat and contributing to adaptation to low-temperature environments, and (3) resisting external pathogens.

RevDate: 2021-08-16
CmpDate: 2021-08-16

Kimball RT, Guido M, Hosner PA, et al (2021)

When good mitochondria go bad: Cyto-nuclear discordance in landfowl (Aves: Galliformes).

Gene, 801:145841.

Mitochondrial sequences were among the first molecular data collected for phylogenetic studies and they are plentiful in DNA sequence archives. However, the future value of mitogenomic data in phylogenetics is uncertain, because its phylogenetic signal sometimes conflicts with that of the nuclear genome. A thorough understanding of the causes and prevalence of cyto-nuclear discordance would aid in reconciling different results owing to sequence data type, and provide a framework for interpreting megaphylogenies when taxa which lack substantial nuclear data are placed using mitochondrial data. Here, we examine the prevalence and possible causes of cyto-nuclear discordance in the landfowl (Aves: Galliformes), leveraging 47 new mitogenomes assembled from off-target reads recovered as part of a target-capture study. We evaluated two hypotheses, that cyto-nuclear discordance is "genuine" and a result of biological processes such as incomplete lineage sorting or introgression, and that cyto-nuclear discordance is an artifact of inaccurate mitochondrial tree estimation (the "inaccurate estimation" hypothesis). We identified seven well-supported topological differences between the mitogenomic tree and trees based on nuclear data. These well-supported topological differences were robust to model selection. An examination of sites suggests these differences were driven by small number of sites, particularly from third-codon positions, suggesting that they were not confounded by convergent directional selection. Hence, the hypothesis of genuine discordance was supported.

RevDate: 2021-07-15

Cheung NJ, John Peter AT, B Kornmann (2021)

Leri: A web-server for identifying protein functional networks from evolutionary couplings.

Computational and structural biotechnology journal, 19:3556-3563.

Information on the co-evolution of amino acid pairs in a protein can be used for endeavors such as protein engineering, mutation design, and structure prediction. Here we report a method that captures significant determinants of proteins using estimated co-evolution information to identify networks of residues, termed "residue communities", relevant to protein function. On the benchmark dataset (67 proteins with both catalytic and allosteric residues), the Pearson's correlation between the identified residues in the communities at functional sites is 0.53, and it is higher than 0.8 by taking account of conserved residues derived from the method. On the endoplasmic reticulum-mitochondria encounter structure complex, the results indicate three distinguishable residue communities that are relevant to functional roles in the protein family, suggesting that the residue communities could be general evolutionary signatures in proteins. Based on the method, we provide a webserver for the scientific community to explore the signatures in protein families, which establishes a powerful tool to analyze residue-level profiling for the discovery of functional sites and biological pathway identification. This web-server is freely available for non-commercial users at, neither login nor e-mail required.

RevDate: 2021-07-14

Husnik F, Tashyreva D, Boscaro V, et al (2021)

Bacterial and archaeal symbioses with protists.

Current biology : CB, 31(13):R862-R877.

Most of the genetic, cellular, and biochemical diversity of life rests within single-celled organisms - the prokaryotes (bacteria and archaea) and microbial eukaryotes (protists). Very close interactions, or symbioses, between protists and prokaryotes are ubiquitous, ecologically significant, and date back at least two billion years ago to the origin of mitochondria. However, most of our knowledge about the evolution and functions of eukaryotic symbioses comes from the study of animal hosts, which represent only a small subset of eukaryotic diversity. Here, we take a broad view of bacterial and archaeal symbioses with protist hosts, focusing on their evolution, ecology, and cell biology, and also explore what functions (if any) the symbionts provide to their hosts. With the immense diversity of protist symbioses starting to come into focus, we can now begin to see how these systems will impact symbiosis theory more broadly.

RevDate: 2021-08-14

Igloi GL (2021)

The Evolutionary Fate of Mitochondrial Aminoacyl-tRNA Synthetases in Amitochondrial Organisms.

Journal of molecular evolution, 89(7):484-493.

During the endosymbiotic evolution of mitochondria, the genes for aminoacyl-tRNA synthetases were transferred to the ancestral nucleus. A further reduction of mitochondrial function resulted in mitochondrion-related organisms (MRO) with a loss of the organelle genome. The fate of the now redundant ancestral mitochondrial aminoacyl-tRNA synthetase genes is uncertain. The derived protein sequence for arginyl-tRNA synthetase from thirty mitosomal organisms have been classified as originating from the ancestral nuclear or mitochondrial gene and compared to the identity element at position 20 of the cognate tRNA that distinguishes the two enzyme forms. The evolutionary choice between loss and retention of the ancestral mitochondrial gene for arginyl-tRNA synthetase reflects the coevolution of arginyl-tRNA synthetase and tRNA identity elements.

RevDate: 2021-08-10
CmpDate: 2021-07-15

Anselmetti Y, El-Mabrouk N, Lafond M, et al (2021)

Gene tree and species tree reconciliation with endosymbiotic gene transfer.

Bioinformatics (Oxford, England), 37(Suppl_1):i120-i132.

MOTIVATION: It is largely established that all extant mitochondria originated from a unique endosymbiotic event integrating an α-proteobacterial genome into an eukaryotic cell. Subsequently, eukaryote evolution has been marked by episodes of gene transfer, mainly from the mitochondria to the nucleus, resulting in a significant reduction of the mitochondrial genome, eventually completely disappearing in some lineages. However, in other lineages such as in land plants, a high variability in gene repertoire distribution, including genes encoded in both the nuclear and mitochondrial genome, is an indication of an ongoing process of Endosymbiotic Gene Transfer (EGT). Understanding how both nuclear and mitochondrial genomes have been shaped by gene loss, duplication and transfer is expected to shed light on a number of open questions regarding the evolution of eukaryotes, including rooting of the eukaryotic tree.

RESULTS: We address the problem of inferring the evolution of a gene family through duplication, loss and EGT events, the latter considered as a special case of horizontal gene transfer occurring between the mitochondrial and nuclear genomes of the same species (in one direction or the other). We consider both EGT events resulting in maintaining (EGTcopy) or removing (EGTcut) the gene copy in the source genome. We present a linear-time algorithm for computing the DLE (Duplication, Loss and EGT) distance, as well as an optimal reconciled tree, for the unitary cost, and a dynamic programming algorithm allowing to output all optimal reconciliations for an arbitrary cost of operations. We illustrate the application of our EndoRex software and analyze different costs settings parameters on a plant dataset and discuss the resulting reconciled trees.

EndoRex implementation and supporting data are available on the GitHub repository via

RevDate: 2021-07-19

Mori MP, Penjweini R, Knutson JR, et al (2021)

Mitochondria and oxygen homeostasis.

The FEBS journal [Epub ahead of print].

Molecular oxygen possesses a dual nature due to its highly reactive free radical property: it is capable of oxidizing metabolic substrates to generate cellular energy, but can also serve as a substrate for genotoxic reactive oxygen species generation. As a labile substance upon which aerobic life depends, the mechanisms for handling cellular oxygen have been fine-tuned and orchestrated in evolution. Protection from atmospheric oxygen toxicity as originally posited by the Endosymbiotic Theory of the Mitochondrion is likely to be one basic principle underlying oxygen homeostasis. We briefly review the literature on oxygen homeostasis both in vitro and in vivo with a focus on the role of the mitochondrion where the majority of cellular oxygen is consumed. The insights gleaned from these basic mechanisms are likely to be important for understanding disease pathogenesis and developing strategies for maintaining health.

RevDate: 2021-07-16
CmpDate: 2021-07-16

Li T, Fang Z, He Q, et al (2021)

Characterizing the Xenoma of Vairimorpha necatrix Provides Insights Into the Most Efficient Mode of Microsporidian Proliferation.

Frontiers in cellular and infection microbiology, 11:699239.

Microsporidia are a group of obligated intracellular parasites that can infect nearly all vertebrates and invertebrates, including humans and economic animals. Microsporidian Vairimorpha necatrix is a natural pathogen of multiple insects and can massively proliferate by making tumor-like xenoma in host tissue. However, little is known about the subcellular structures of this xenoma and the proliferation features of the pathogens inside. Here, we characterized the V. necatrix xenoma produced in muscle cells of silkworm midgut. In result, the whitish xenoma was initially observed on the 12th day post infection on the outer surface of the midgut and later became larger and numerous. The observation by scanning electronic microscopy showed that the xenoma is mostly elliptical and spindle with dense pathogen-containing protrusions and spores on the surface, which were likely shedding off the xenoma through exocytosis and could be an infection source of other tissues. Demonstrated with transmission electron microscopy and fluorescent staining, the xenoma was enveloped by a monolayer membrane, and full of vesicle structures, mitochondria, and endoplasmic reticulum around parasites in development, suggesting that high level of energy and nutrients were produced to support the massive proliferation of the parasites. Multiple hypertrophic nuclei were found in one single xenoma, indicating that the cyst was probably formed by fusion of multiple muscle cells. Observed by fluorescence in situ hybridization, pathogens in the xenoma were in merongony, sporogony, and octosporogony, and mature stages. And mature spores were pushed to the center while vegetative pathogens were in the surface layer of the xenoma. The V. necatrix meront usually contained two to three nuclei, and sporont contained two nuclei and was wrapped by a thick membrane with high electron density. The V. necatrix sporogony produces two types of spores, the ordinary dikaryotic spore and unicellular octospores, the latter of which were smaller in size and packed in a sporophorous vesicle. In summary, V. necatrix xenoma is a specialized cyst likely formed by fusion of multiple muscle cells and provides high concentration of energy and nutrients with increased number of mitochondria and endoplasmic reticulum for the massive proliferation of pathogens inside.

RevDate: 2021-07-03

Sheng L, Zhou T, Shi Z, et al (2021)

The complete mitochondrial genome of Trictenotoma davidi Deyrolle, 1875 (Coleoptera: Trictenotomidae).

Mitochondrial DNA. Part B, Resources, 6(7):2026-2027.

Trictenotoma davidi Deyrolle, 1875 is a beetle of the Trictenotomidae family. The length of the complete mitochondria genome of T. davidi was 15,910 bp with 24.1% GC content, including 39.9% A, 15.1% C, 9.0% G, and 36.0% T. The genome encoded 13 protein-coding genes, 22 tRNAs, and 2 rRNAs. Phylogenetic analysis showed that T. davidi was closely related to Vincenzellus ruficollis. This study provided useful genetic information for the evolution of T. davidi and Trictenotomidae insects.

RevDate: 2021-07-03

Degli Esposti M, Moya-Beltrán A, Quatrini R, et al (2021)

Respiratory Heme A-Containing Oxidases Originated in the Ancestors of Iron-Oxidizing Bacteria.

Frontiers in microbiology, 12:664216.

Respiration is a major trait shaping the biology of many environments. Cytochrome oxidase containing heme A (COX) is a common terminal oxidase in aerobic bacteria and is the only one in mammalian mitochondria. The synthesis of heme A is catalyzed by heme A synthase (CtaA/Cox15), an enzyme that most likely coevolved with COX. The evolutionary origin of COX in bacteria has remained unknown. Using extensive sequence and phylogenetic analysis, we show that the ancestral type of heme A synthases is present in iron-oxidizing Proteobacteria such as Acidithiobacillus spp. These bacteria also contain a deep branching form of the major COX subunit (COX1) and an ancestral variant of CtaG, a protein that is specifically required for COX biogenesis. Our work thus suggests that the ancestors of extant iron-oxidizers were the first to evolve COX. Consistent with this conclusion, acidophilic iron-oxidizing prokaryotes lived on emerged land around the time for which there is the earliest geochemical evidence of aerobic respiration on earth. Hence, ecological niches of iron oxidation have apparently promoted the evolution of aerobic respiration.

RevDate: 2021-07-03

García-Casas P, Alvarez-Illera P, Gómez-Orte E, et al (2021)

The Mitochondrial Na+/Ca2+ Exchanger Inhibitor CGP37157 Preserves Muscle Structure and Function to Increase Lifespan and Healthspan in Caenorhabditis elegans.

Frontiers in pharmacology, 12:695687.

We have reported recently that the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 extends lifespan in Caenorhabditis elegans by a mechanism involving mitochondria, the TOR pathway and the insulin/IGF1 pathway. Here we show that CGP37157 significantly improved the evolution with age of the sarcomeric regular structure, delaying development of sarcopenia in C. elegans body wall muscle and increasing the average and maximum speed of the worms. Similarly, CGP37157 favored the maintenance of a regular mitochondrial structure during aging. We have also investigated further the mechanism of the effect of CGP37157 by studying its effect in mutants of aak-1;aak-2/AMP-activated kinase, sir-2.1/sirtuin, rsks-1/S6 kinase and daf-16/FOXO. We found that this compound was still effective increasing lifespan in all these mutants, indicating that these pathways are not involved in the effect. We have then monitored pharynx cytosolic and mitochondrial Ca2+ signalling and our results suggest that CGP37157 is probably inhibiting not only the mitochondrial Na+/Ca2+ exchanger, but also Ca2+ entry through the plasma membrane. Finally, a transcriptomic study detected that CGP37157 induced changes in lipid metabolism enzymes and a four-fold increase in the expression of ncx-6, one of the C. elegans mitochondrial Na+/Ca2+ exchangers. In summary, CGP37157 increases both lifespan and healthspan by a mechanism involving changes in cytosolic and mitochondrial Ca2+ homeostasis. Thus, Ca2+ signalling could be a promising target to act on aging.

RevDate: 2021-07-16
CmpDate: 2021-07-16

Richtová J, Sheiner L, Gruber A, et al (2021)

Using Diatom and Apicomplexan Models to Study the Heme Pathway of Chromera velia.

International journal of molecular sciences, 22(12):.

Heme biosynthesis is essential for almost all living organisms. Despite its conserved function, the pathway's enzymes can be located in a remarkable diversity of cellular compartments in different organisms. This location does not always reflect their evolutionary origins, as might be expected from the history of their acquisition through endosymbiosis. Instead, the final subcellular localization of the enzyme reflects multiple factors, including evolutionary origin, demand for the product, availability of the substrate, and mechanism of pathway regulation. The biosynthesis of heme in the apicomonad Chromera velia follows a chimeric pathway combining heme elements from the ancient algal symbiont and the host. Computational analyses using different algorithms predict complex targeting patterns, placing enzymes in the mitochondrion, plastid, endoplasmic reticulum, or the cytoplasm. We employed heterologous reporter gene expression in the apicomplexan parasite Toxoplasma gondii and the diatom Phaeodactylum tricornutum to experimentally test these predictions. 5-aminolevulinate synthase was located in the mitochondria in both transfection systems. In T. gondii, the two 5-aminolevulinate dehydratases were located in the cytosol, uroporphyrinogen synthase in the mitochondrion, and the two ferrochelatases in the plastid. In P. tricornutum, all remaining enzymes, from ALA-dehydratase to ferrochelatase, were placed either in the endoplasmic reticulum or in the periplastidial space.

RevDate: 2021-07-27

Purnomo GA, Mitchell KJ, O'Connor S, et al (2021)

Mitogenomes Reveal Two Major Influxes of Papuan Ancestry across Wallacea Following the Last Glacial Maximum and Austronesian Contact.

Genes, 12(7):.

The tropical archipelago of Wallacea contains thousands of individual islands interspersed between mainland Asia and Near Oceania, and marks the location of a series of ancient oceanic voyages leading to the peopling of Sahul-i.e., the former continent that joined Australia and New Guinea at a time of lowered sea level-by 50,000 years ago. Despite the apparent deep antiquity of human presence in Wallacea, prior population history research in this region has been hampered by patchy archaeological and genetic records and is largely concentrated upon more recent history that follows the arrival of Austronesian seafarers ~3000-4000 years ago (3-4 ka). To shed light on the deeper history of Wallacea and its connections with New Guinea and Australia, we performed phylogeographic analyses on 656 whole mitogenomes from these three regions, including 186 new samples from eight Wallacean islands and three West Papuan populations. Our results point to a surprisingly dynamic population history in Wallacea, marked by two periods of extensive demographic change concentrated around the Last Glacial Maximum ~15 ka and post-Austronesian contact ~3 ka. These changes appear to have greatly diminished genetic signals informative about the original peopling of Sahul, and have important implications for our current understanding of the population history of the region.

RevDate: 2021-08-25

Amine AAA, Liao CW, Hsu PC, et al (2021)

Experimental evolution improves mitochondrial genome quality control in Saccharomyces cerevisiae and extends its replicative lifespan.

Current biology : CB, 31(16):3663-3670.e4.

The mitochondrion is an ancient endosymbiotic organelle that performs many essential functions in eukaryotic cells.1-3 Mitochondrial impairment often results in physiological defects or diseases.2-8 Since most mitochondrial genes have been copied into the nuclear genome during evolution,9 the regulatory and interaction mechanisms between the mitochondrial and nuclear genomes are very complex. Multiple mechanisms, including antioxidant, DNA repair, mitophagy, and mitochondrial biogenesis pathways, have been shown to monitor the quality and quantity of mitochondria.10-12 Nonetheless, it remains unclear if these pathways can be further modified to enhance mitochondrial stability. Previously, experimental evolution has been used to adapt cells to novel growth conditions. By analyzing the resulting evolved populations, insights have been gained into the underlying molecular mechanisms.13 Here, we experimentally evolved yeast cells under conditions that selected for efficient respiration while continuously assaulting the mitochondrial genome (mtDNA) with ethidium bromide (EtBr). We found that the ability to maintain functional mtDNA was enhanced in most of the evolved lines when challenged with mtDNA-damaging reagents. We identified mutations of the mitochondrial NADH dehydrogenase NDE1 in most of the evolved lines, but other pathways are also involved. Finally, we show that cells displaying enhanced mtDNA retention also exhibit a prolonged replicative lifespan. Our work reveals potential evolutionary trajectories by which cells can maintain functional mitochondria in response to mtDNA stress, as well as the physiological implications of such adaptations.

RevDate: 2021-07-01

Yang M, Dong D, X Li (2021)

The complete mitogenome of Phymorhynchus sp. (Neogastropoda, Conoidea, Raphitomidae) provides insights into the deep-sea adaptive evolution of Conoidea.

Ecology and evolution, 11(12):7518-7531.

The deep-sea environment is characterized by darkness, hypoxia, and high hydrostatic pressure. Mitochondria play a vital role in energy metabolism; thus, they may endure the selection process during the adaptive evolution of deep-sea organisms. In the present study, the mitogenome of Phymorhynchus sp. from the Haima methane seep was completely assembled and characterized. This mitogenome is 16,681 bp in length and contains 13 protein-coding genes, 2 rRNAs, and 22 tRNAs. The gene order and orientation were identical to those of most sequenced conoidean gastropods. Some special elements, such as tandem repeat sequences and AT-rich sequences, which are involved in the regulation of the replication and transcription of the mitogenome, were observed in the control region. Phylogenetic analysis revealed that Conoidea is divided into two separate clades with high nodal support. Positive selection analysis revealed evidence of adaptive changes in the mitogenomes of deep-sea conoidean gastropods. Eight residues located in atp6, cox1, cytb, nad1, nad4, and nad5 were determined to have undergone positive selection. This study explores the adaptive evolution of deep-sea conoidean gastropods and provides valuable clues at the mitochondrial level regarding the exceptional adaptive ability of organisms in deep-sea environments.

RevDate: 2021-07-26
CmpDate: 2021-07-26

Lin C, Tang D, Gao X, et al (2021)

Molecular characterization, dynamic transcription, and potential function of KIF3A/KIF3B during spermiogenesis in Opsariichthys bidens.

Gene, 798:145795.

Spermiogenesis is the final phase of spermatogenesis, wherein the spermatids differentiate into mature spermatozoa via complex morphological transformation. In this process, kinesin plays an important role. Here, we observed the morphological transformation of spermatids and analyzed the characterization, dynamic transcription, and potential function of kinesin KIF3A/KIF3B during spermiogenesis in Chinese hook snout carp (Opsariichthys bidens). We found that the full-length cDNAs of O. bidens kif3a and kif3b were 2544 and 2806 bp in length comprising 119 bp and 259 bp 5' untranslated region (UTR), 313 bp and 222 bp 3' UTR, and 2112 bp and 2325 bp open reading frame encoding 703 and 774 amino acids, respectively. Ob-KIF3A/KIF3B proteins have three domains, namely N-terminal head, coiled-coil stalk, and C-terminal tail, and exhibit high similarity with homologous proteins in vertebrates and invertebrates. Ob-kif3a/kif3b mRNAs were ubiquitously expressed in all tissues examined, with the highest expression in the brain and stage-IV testis. Immunofluorescence results showed that Ob-KIF3A was co-localized with tubulin and the mitochondria. Particularly, in early spermatids, Ob-KIF3A, tubulin, and the mitochondrial signals were evenly distributed in the cytoplasm, whereas in middle spermatids, they were distributed around the nucleus. In the late stage, the signals were concentrated on one side of the nucleus, where the tail is formed, whereas in mature sperms, they were detected in the midpiece and flagellum. These results indicate that Ob-KIF3A/KIF3B may participate in nuclear reshaping, flagellum formation, and mitochondrial aggregation in the midpiece during spermiogenesis.

RevDate: 2021-09-13
CmpDate: 2021-09-13

Iwata R, P Vanderhaeghen (2021)

Regulatory roles of mitochondria and metabolism in neurogenesis.

Current opinion in neurobiology, 69:231-240.

Neural stem cells (NSCs) undergo massive molecular and cellular changes during neuronal differentiation. These include mitochondria and metabolism remodelling, which were thought to be mostly permissive cues, but recent work indicates that they are causally linked to neurogenesis. Striking remodelling of mitochondria occurs right after mitosis of NSCs, which influences the postmitotic daughter cells towards self-renewal or differentiation. The transitioning to neuronal fate requires metabolic rewiring including increased oxidative phosphorylation activity, which drives transcriptional and epigenetic effects to influence cell fate. Mitochondria metabolic pathways also contribute in an essential way to the regulation of NSC proliferation and self-renewal. The influence of mitochondria and metabolism on neurogenesis is conserved from fly to human systems, but also displays striking differences linked to cell context or species. These new findings have important implications for our understanding of neurodevelopmental diseases and possibly human brain evolution.

RevDate: 2021-08-18
CmpDate: 2021-08-18

Xu XD, Guan JY, Zhang ZY, et al (2021)

Novel tRNA gene rearrangements in the mitochondrial genomes of praying mantises (Mantodea: Mantidae): Translocation, duplication and pseudogenization.

International journal of biological macromolecules, 185:403-411.

Gene rearrangements have been found in several mitochondrial genomes of Mantodea, located in the gene blocks CR-I-Q-M-ND2, COX1-K-D-ATP8 and ND3-A-R-N-S-E-F-ND5. We have sequenced one mitogenome of Amelidae (Yersinia mexicana) and six mitogenomes of Mantidae to discuss the mitochondrial gene rearrangement and the phylogenetic relationship within Mantidae. These mitogenomes showed rearrangements of tRNA genes except for Asiadodis yunnanensis and Hierodula zhangi. These novel gene rearrangements of Mantidae were primarily concentrated in the region of CR-I-Q-M-ND2, including gene translocation, duplication and pseudogenization. For the occurrences of these rearrangements, the tandem duplication-random loss (TDRL) model and slipped-strand mispairing model were suitable to explain. Large non-coding regions (LNCRs) located in the region of CR-I-Q-M-ND2 were detected in most Mantidae species, whereas some LNCRs had high similarity to the control region (CR). Both BI and ML phylogenetic analyses supported the monophyly of Mantidae and the paraphyly of Mantinae. The phylogenetic results with the gene order and the location of NCRs acted as forceful evidence that specific gene rearrangements and special LNCRs may be synapomorphies for several groups of mantises.

RevDate: 2021-07-10
CmpDate: 2021-07-05

Evers F, Cabrera-Orefice A, Elurbe DM, et al (2021)

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.

Nature communications, 12(1):3820.

Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

RevDate: 2021-08-09

Dymek AM, Pecio A, RP Piprek (2021)

Diversity of Balbiani body formation in internally and externally fertilizing representatives of Osteoglossiformes (Teleostei: Osteoglossomorpha).

Journal of morphology, 282(9):1313-1329.

During the early stages of oogenesis, the Balbiani body is formed in the primary oocytes. It consists of the Golgi apparatus, endoplasmic reticulum (ER), and numerous mitochondria aggregated with germ plasm, but its form may differ among animals. Hypothetically, during oogenesis oocytes become adapted to future development in two different environments depending on internal or external fertilization. We aimed to investigate, using light and transmission electron microscopy, the development of the Balbiani body during oogenesis in representatives of Osteoglossiformes, one of the most basal Teleostei groups. We analyzed the structure of oogonia and primary oocytes in the internally fertilizing butterflyfish Pantodon buchholzi and the externally fertilizing Osteoglossum bicirrhosum and Arapaima gigas to compare formation of the Balbiani body in relation to modes of fertilization. We demonstrated that the presence of the germ plasm as well as the fusion and fission of mitochondria are the conserved features of the Bb. However, each species exhibited also some peculiar features, including the presence of three types of ooplasm with different electron density and mitochondria-associated membranes in P. buchholzi; annulate lamellae, complexes of the Golgi apparatus, ER network, and lysosome-like bodies in O. bicirrhosum; as well as karmellae and whorls formed by the lamellae of the ER in A. gigas. Moreover, the form of the germ plasm observed in close contact with mitochondria differed between osteoglossiforms, with a "net-like" structure in P. buchholzi, the presence of numerous strings in O. bicirrhosum, and irregular accumulations in A. gigas. These unique features indicate that the extreme diversity of gamete structure observed so far only in the spermatozoa of osteoglossiforms is also characteristic for oocyte development in these basal teleosts. Possible reason of this variability is a period of about 150 million years of independent evolution of the lineages.

RevDate: 2021-07-07
CmpDate: 2021-07-07

Jin L, Tang Q, Hu S, et al (2021)

A pig BodyMap transcriptome reveals diverse tissue physiologies and evolutionary dynamics of transcription.

Nature communications, 12(1):3715.

A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter-enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits.

RevDate: 2021-06-19

Gažová I, Lefevre L, Bush SJ, et al (2021)

CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1.

Frontiers in cell and developmental biology, 9:679544.

USP16 is a histone deubiquitinase which facilitates G2/M transition during the cell cycle, regulates DNA damage repair and contributes to inducible gene expression. We mutated the USP16 gene in a high differentiation clone of the acute monocytic leukemia cell line THP-1 using the CRISPR-Cas9 system and generated four homozygous knockout clones. All were able to proliferate and to differentiate in response to phorbol ester (PMA) treatment. One line was highly proliferative prior to PMA treatment and shut down proliferation upon differentiation, like wild type. Three clones showed sustained expression of the progenitor cell marker MYB, indicating that differentiation had not completely blocked proliferation in these clones. Network analysis of transcriptomic differences among wild type, heterozygotes and homozygotes showed clusters of genes that were up- or down-regulated after differentiation in all cell lines. Prior to PMA treatment, the homozygous clones had lower levels than wild type of genes relating to metabolism and mitochondria, including SRPRB, encoding an interaction partner of USP16. There was also apparent loss of interferon signaling. In contrast, a number of genes were up-regulated in the homozygous cells compared to wild type at baseline, including other deubiquitinases (USP12, BAP1, and MYSM1). However, three homozygotes failed to fully induce USP3 during differentiation. Other network clusters showed effects prior to or after differentiation in the homozygous clones. Thus the removal of USP16 affected the transcriptome of the cells, although all these lines were able to survive, which suggests that the functions attributed to USP16 may be redundant. Our analysis indicates that the leukemic line can adapt to the extreme selection pressure applied by the loss of USP16, and the harsh conditions of the gene editing and selection protocol, through different compensatory pathways. Similar selection pressures occur during the evolution of a cancer in vivo, and our results can be seen as a case study in leukemic cell adaptation. USP16 has been considered a target for cancer chemotherapy, but our results suggest that treatment would select for escape mutants that are resistant to USP16 inhibitors.

RevDate: 2021-07-24

Cadena LR, Gahura O, Panicucci B, et al (2021)

Mitochondrial Contact Site and Cristae Organization System and F1FO-ATP Synthase Crosstalk Is a Fundamental Property of Mitochondrial Cristae.

mSphere [Epub ahead of print].

Mitochondrial cristae are polymorphic invaginations of the inner membrane that are the fabric of cellular respiration. Both the mitochondrial contact site and cristae organization system (MICOS) and the F1FO-ATP synthase are vital for sculpting cristae by opposing membrane-bending forces. While MICOS promotes negative curvature at crista junctions, dimeric F1FO-ATP synthase is crucial for positive curvature at crista rims. Crosstalk between these two complexes has been observed in baker's yeast, the model organism of the Opisthokonta supergroup. Here, we report that this property is conserved in Trypanosoma brucei, a member of the Discoba clade that separated from the Opisthokonta ∼2 billion years ago. Specifically, one of the paralogs of the core MICOS subunit Mic10 interacts with dimeric F1FO-ATP synthase, whereas the other core Mic60 subunit has a counteractive effect on F1FO-ATP synthase oligomerization. This is evocative of the nature of MICOS-F1FO-ATP synthase crosstalk in yeast, which is remarkable given the diversification that these two complexes have undergone during almost 2 eons of independent evolution. Furthermore, we identified a highly diverged, putative homolog of subunit e, which is essential for the stability of F1FO-ATP synthase dimers in yeast. Just like subunit e, it is preferentially associated with dimers and interacts with Mic10, and its silencing results in severe defects to cristae and the disintegration of F1FO-ATP synthase dimers. Our findings indicate that crosstalk between MICOS and dimeric F1FO-ATP synthase is a fundamental property impacting crista shape throughout eukaryotes. IMPORTANCE Mitochondria have undergone profound diversification in separate lineages that have radiated since the last common ancestor of eukaryotes some eons ago. Most eukaryotes are unicellular protists, including etiological agents of infectious diseases, like Trypanosoma brucei. Thus, the study of a broad range of protists can reveal fundamental features shared by all eukaryotes and lineage-specific innovations. Here, we report that two different protein complexes, MICOS and F1FO-ATP synthase, known to affect mitochondrial architecture, undergo crosstalk in T. brucei, just as in baker's yeast. This is remarkable considering that these complexes have otherwise undergone many changes during their almost 2 billion years of independent evolution. Thus, this crosstalk is a fundamental property needed to maintain proper mitochondrial structure even if the constituent players considerably diverged.

RevDate: 2021-07-07

Hoshino Y, EA Gaucher (2021)

Evolution of bacterial steroid biosynthesis and its impact on eukaryogenesis.

Proceedings of the National Academy of Sciences of the United States of America, 118(25):.

Steroids are components of the eukaryotic cellular membrane and have indispensable roles in the process of eukaryotic endocytosis by regulating membrane fluidity and permeability. In particular, steroids may have been a structural prerequisite for the acquisition of mitochondria via endocytosis during eukaryogenesis. While eukaryotes are inferred to have evolved from an archaeal lineage, there is little similarity between the eukaryotic and archaeal cellular membranes. As such, the evolution of eukaryotic cellular membranes has limited our understanding of eukaryogenesis. Despite evolving from archaea, the eukaryotic cellular membrane is essentially a fatty acid bacterial-type membrane, which implies a substantial bacterial contribution to the evolution of the eukaryotic cellular membrane. Here, we address the evolution of steroid biosynthesis in eukaryotes by combining ancestral sequence reconstruction and comprehensive phylogenetic analyses of steroid biosynthesis genes. Contrary to the traditional assumption that eukaryotic steroid biosynthesis evolved within eukaryotes, most steroid biosynthesis genes are inferred to be derived from bacteria. In particular, aerobic deltaproteobacteria (myxobacteria) seem to have mediated the transfer of key genes for steroid biosynthesis to eukaryotes. Analyses of resurrected steroid biosynthesis enzymes suggest that the steroid biosynthesis pathway in early eukaryotes may have been similar to the pathway seen in modern plants and algae. These resurrected proteins also experimentally demonstrate that molecular oxygen was required to establish the modern eukaryotic cellular membrane during eukaryogenesis. Our study provides unique insight into relationships between early eukaryotes and other bacteria in addition to the well-known endosymbiosis with alphaproteobacteria.

RevDate: 2021-08-17
CmpDate: 2021-08-17

Mixão V, Hegedűsová E, Saus E, et al (2021)

Genome analysis of Candida subhashii reveals its hybrid nature and dual mitochondrial genome conformations.

DNA research : an international journal for rapid publication of reports on genes and genomes, 28(3):.

Candida subhashii belongs to the CUG-Ser clade, a group of phylogenetically closely related yeast species that includes some human opportunistic pathogens, such as Candida albicans. Despite being present in the environment, C. subhashii was initially described as the causative agent of a case of peritonitis. Considering the relevance of whole-genome sequencing and analysis for our understanding of genome evolution and pathogenicity, we sequenced, assembled and annotated the genome of C. subhashii type strain. Our results show that C. subhashii presents a highly heterozygous genome and other signatures that point to a hybrid ancestry. The presence of functional pathways for assimilation of hydroxyaromatic compounds goes in line with the affiliation of this yeast with soil microbial communities involved in lignin decomposition. Furthermore, we observed that different clones of this strain may present circular or linear mitochondrial DNA. Re-sequencing and comparison of strains with differential mitochondrial genome topology revealed five candidate genes potentially associated with this conformational change: MSK1, SSZ1, ALG5, MRPL9 and OYE32.

RevDate: 2021-06-21

Manoj KM, NM Bazhin (2021)

The murburn precepts for aerobic respiration and redox homeostasis.

Progress in biophysics and molecular biology pii:S0079-6107(21)00060-2 [Epub ahead of print].

Murburn concept is a new perspective to metabolism which posits that certain redox enzymes/proteins mediate catalysis outside their active site, via diffusible reactive oxygen species (DROS, usually deemed as toxic wastes). We have recently questioned the proton-centric chemiosmotic rotary ATP synthesis (CRAS) explanation for mitochondrial oxidative phosphorylation (mOxPhos) and proposed an oxygen-centric murburn model in lieu. Herein, the chemical equations and thermodynamic foundations for this new model of mOxPhos are detailed. Standard transformed Gibbs free energy values of respiratory reactions are calculated to address the spontaneity, control, and efficiency of oxidative phosphorylation. Unlike the deterministic/multi-molecular and 'irreducibly complex' CRAS model, the stochastic/bimolecular and parsimonious murburn reactions afford a more viable precept for the variable and non-integral stoichiometry, higher yield for NADH than FADH2, and origin/evolution of oxygen-centric cellular life. Also, we present tangible DROS-based explanations for the multiple roles of various reaction components, HCN > H2S order of cellular toxicity in aerobes, and explain why oxygen inhibits anaerobes. We highlight the thermodynamic significance of proton deficiency in NADH/mitochondria and link the 'oxygen → DROS → water' metabolic pathway to the macroscopic physiologies of ATP-synthesis, trans-membrane potential, thermogenesis, and homeostasis. We also provide arguments for the extension of the murburn bioenergetics model to life under anoxic and extreme/unique habitats. In the context of mOxPhos, our findings imply that DROS should be seen as an essential requisite for life, and not merely as pathophysiological manifestations.

RevDate: 2021-09-22

Capitanio G, Papa F, S Papa (2021)

The allosteric protein interactions in the proton-motive function of mammalian redox enzymes of the respiratory chain.

Biochimie, 189:1-12.

Insight into mammalian respiratory complexes defines the role of allosteric protein interactions in their proton-motive activity. In cytochrome c oxidase (CxIV) conformational change of subunit I, caused by O2 binding to heme a32+-CuB+ and reduction, and stereochemical transitions coupled to oxidation/reduction of heme a and CuA, combined with electrostatic effects, determine the proton pumping activity. In ubiquinone-cytochrome c oxidoreductase (CxIII) conformational movement of Fe-S protein between cytochromes b and c1 is the key element of the proton-motive activity. In NADH-ubiquinone oxidoreductase (CxI) ubiquinone binding and reduction result in conformational changes of subunits in the quinone reaction structure which initiate proton pumping.

RevDate: 2021-06-18
CmpDate: 2021-06-18

Mazzocca A, S Fais (2021)

New hypotheses for cancer generation and progression.

Medical hypotheses, 152:110614.

Since Nixon famously declared war on cancer in 1971, trillions of dollars have been spent on cancer research but the life expectancy for most forms of cancer is still poor. There are many reasons for the partial success of cancer translational research. One of these can be the predominance of certain paradigms that potentially narrowed the vision in interpreting cancer. The main paradigm to explain carcinogenesis is based on DNA mutations, which is well interpreted by the somatic mutation theory (SMT). However, a different theory claims that cancer is instead a tissue disease as proposed by the Tissue Organization Field Theory (TOFT). Here, we propose new hypotheses to explain the origin and pathogenesis of cancer. In this perspective, the systemic-evolutionary theory of cancer (SETOC) is discussed as well as how the microenvironment affects the adaptation of transformed cells and the reversion to a unicellular-like or embryo-like phenotype.

RevDate: 2021-06-11
CmpDate: 2021-06-11

Wang S, H Luo (2021)

Dating Alphaproteobacteria evolution with eukaryotic fossils.

Nature communications, 12(1):3324.

Elucidating the timescale of the evolution of Alphaproteobacteria, one of the most prevalent microbial lineages in marine and terrestrial ecosystems, is key to testing hypotheses on their co-evolution with eukaryotic hosts and Earth's systems, which, however, is largely limited by the scarcity of bacterial fossils. Here, we incorporate eukaryotic fossils to date the divergence times of Alphaproteobacteria, based on the mitochondrial endosymbiosis that mitochondria evolved from an alphaproteobacterial lineage. We estimate that Alphaproteobacteria arose ~1900 million years (Ma) ago, followed by rapid divergence of their major clades. We show that the origin of Rickettsiales, an order of obligate intracellular bacteria whose hosts are mostly animals, predates the emergence of animals for ~700 Ma but coincides with that of eukaryotes. This, together with reconstruction of ancestral hosts, strongly suggests that early Rickettsiales lineages had established previously underappreciated interactions with unicellular eukaryotes. Moreover, the mitochondria-based approach displays higher robustness to uncertainties in calibrations compared with the traditional strategy using cyanobacterial fossils. Further, our analyses imply the potential of dating the (bacterial) tree of life based on endosymbiosis events, and suggest that previous applications using divergence times of the modern hosts of symbiotic bacteria to date bacterial evolution might need to be revisited.

RevDate: 2021-06-27

Cramer ERA, Garcia-Del-Rey E, Johannessen LE, et al (2021)

Longer Sperm Swim More Slowly in the Canary Islands Chiffchaff.

Cells, 10(6):.

Sperm swimming performance affects male fertilization success, particularly in species with high sperm competition. Understanding how sperm morphology impacts swimming performance is therefore important. Sperm swimming speed is hypothesized to increase with total sperm length, relative flagellum length (with the flagellum generating forward thrust), and relative midpiece length (as the midpiece contains the mitochondria). We tested these hypotheses and tested for divergence in sperm traits in five island populations of Canary Islands chiffchaff (Phylloscopus canariensis). We confirmed incipient mitochondrial DNA differentiation between Gran Canaria and the other islands. Sperm swimming speed correlated negatively with total sperm length, did not correlate with relative flagellum length, and correlated negatively with relative midpiece length (for Gran Canaria only). The proportion of motile cells increased with relative flagellum length on Gran Canaria only. Sperm morphology was similar across islands. We thus add to a growing number of studies on passerine birds that do not support sperm morphology-swimming speed hypotheses. We suggest that the swimming mechanics of passerine sperm are sufficiently different from mammalian sperm that predictions from mammalian hydrodynamic models should no longer be applied for this taxon. While both sperm morphology and sperm swimming speed are likely under selection in passerines, the relationship between them requires further elucidation.

RevDate: 2021-06-21
CmpDate: 2021-06-21

Dür A, Huber N, W Parson (2021)

Fine-Tuning Phylogenetic Alignment and Haplogrouping of mtDNA Sequences.

International journal of molecular sciences, 22(11):.

In this paper, we present a new algorithm for alignment and haplogroup estimation of mitochondrial DNA (mtDNA) sequences. Based on 26,011 vetted full mitogenome sequences, we refined the 5435 original haplogroup motifs of Phylotree Build 17 without changing the haplogroup nomenclature. We adapted 430 motifs (about 8%) and added 966 motifs for yet undetermined subclades. In summary, this led to an 18% increase of haplogroup defining motifs for full mitogenomes and a 30% increase for the mtDNA control region that is of interest for a variety of scientific disciplines, such as medical, population and forensic genetics. The new algorithm is implemented in the EMPOP mtDNA database and is freely accessible.

RevDate: 2021-06-24
CmpDate: 2021-06-24

Ai D, Peng L, Qin D, et al (2021)

Characterization of Three Complete Mitogenomes of Flatidae (Hemiptera: Fulgoroidea) and Compositional Heterogeneity Analysis in the Planthoppers' Mitochondrial Phylogenomics.

International journal of molecular sciences, 22(11):.

Although sequences of mitogenomes have been widely used for investigating phylogenetic relationship, population genetics, and biogeography in many members of Fulgoroidea, only one complete mitogenome of a member of Flatidae has been sequenced. Here, the complete mitogenomes of Cerynia lineola, Cromna sinensis, and Zecheuna tonkinensis are sequenced. The gene arrangements of the three new mitogenomes are consistent with ancestral insect mitogenomes. The strategy of using mitogenomes in phylogenetics remains in dispute due to the heterogeneity in base composition and the possible variation in evolutionary rates. In this study, we found compositional heterogeneity and variable evolutionary rates among planthopper mitogenomes. Phylogenetic analysis based on site-homogeneous models showed that the families (Delphacidae and Derbidae) with high values of Ka/Ks and A + T content tended to fall together at a basal position on the trees. Using a site-heterogeneous mixture CAT + GTR model implemented in PhyloBayes yielded almost the same topology. Our results recovered the monophyly of Fulgoroidea. In this study, we apply the heterogeneous mixture model to the planthoppers' phylogenetic analysis for the first time. Our study is based on a large sample and provides a methodological reference for future phylogenetic studies of Fulgoroidea.

RevDate: 2021-06-17
CmpDate: 2021-06-17

Di Gregorio E, Miolo G, Saorin A, et al (2021)

From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy.

International journal of molecular sciences, 22(11):.

Over the last decades, the study of cancer metabolism has returned to the forefront of cancer research and challenged the role of genetics in the understanding of cancer development. One of the major impulses of this new trend came from the discovery of oncometabolites, metabolic intermediates whose abnormal cellular accumulation triggers oncogenic signalling and tumorigenesis. These findings have led to reconsideration and support for the long-forgotten hypothesis of Warburg of altered metabolism as oncogenic driver of cancer and started a novel paradigm whereby mitochondrial metabolites play a pivotal role in malignant transformation. In this review, we describe the evolution of the cancer metabolism research from a historical perspective up to the oncometabolites discovery that spawned the new vision of cancer as a metabolic disease. The oncometabolites' mechanisms of cellular transformation and their contribution to the development of new targeted cancer therapies together with their drawbacks are further reviewed and discussed.

RevDate: 2021-06-05

Yamaguchi K, Kitamura S, Furutake Y, et al (2021)

Acquired Evolution of Mitochondrial Metabolism Regulated by HNF1B in Ovarian Clear Cell Carcinoma.

Cancers, 13(10):.

Clear cell carcinoma (CCC) of the ovary exhibits a unique morphology and clinically malignant behavior. The eosinophilic cytoplasm includes abundant glycogen. Although the growth is slow, the prognosis is poor owing to resistance to conventional chemotherapies. CCC often arises in endometriotic cysts and is accompanied by endometriosis. Based on these characteristics, three clinical questions are considered: why does ovarian cancer, especially CCC and endometrioid carcinoma, frequently occur in endometriotic cysts, why do distinct histological subtypes (CCC and endometrioid carcinoma) arise in the endometriotic cyst, and why does ovarian CCC possess unique characteristics? Mutations in AT-rich interacting domain-containing protein 1A and phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit alpha genes may contribute to the carcinogenesis of ovarian CCC, whereas hepatocyte nuclear factor-1-beta (HNF1B) plays crucial roles in sculpting the unique characteristics of ovarian CCC through metabolic alterations. HNF1B increases glutathione synthesis, activates anaerobic glycolysis called the Warburg effect, and suppresses mitochondria. These metabolic changes may be induced in stressful environments. Life has evolved to utilize and control energy; eukaryotes require mitochondria to transform oxygen reduction into useful energy. Because mitochondrial function is suppressed in ovarian CCC, these cancer cells probably acquired further metabolic evolution during the carcinogenic process in order to survive stressful environments.

RevDate: 2021-06-15

Lyu D, Msimbira LA, Nazari M, et al (2021)

The Coevolution of Plants and Microbes Underpins Sustainable Agriculture.

Microorganisms, 9(5):.

Terrestrial plants evolution occurred in the presence of microbes, the phytomicrobiome. The rhizosphere microbial community is the most abundant and diverse subset of the phytomicrobiome and can include both beneficial and parasitic/pathogenic microbes. Prokaryotes of the phytomicrobiome have evolved relationships with plants that range from non-dependent interactions to dependent endosymbionts. The most extreme endosymbiotic examples are the chloroplasts and mitochondria, which have become organelles and integral parts of the plant, leading to some similarity in DNA sequence between plant tissues and cyanobacteria, the prokaryotic symbiont of ancestral plants. Microbes were associated with the precursors of land plants, green algae, and helped algae transition from aquatic to terrestrial environments. In the terrestrial setting the phytomicrobiome contributes to plant growth and development by (1) establishing symbiotic relationships between plant growth-promoting microbes, including rhizobacteria and mycorrhizal fungi, (2) conferring biotic stress resistance by producing antibiotic compounds, and (3) secreting microbe-to-plant signal compounds, such as phytohormones or their analogues, that regulate aspects of plant physiology, including stress resistance. As plants have evolved, they recruited microbes to assist in the adaptation to available growing environments. Microbes serve themselves by promoting plant growth, which in turn provides microbes with nutrition (root exudates, a source of reduced carbon) and a desirable habitat (the rhizosphere or within plant tissues). The outcome of this coevolution is the diverse and metabolically rich microbial community that now exists in the rhizosphere of terrestrial plants. The holobiont, the unit made up of the phytomicrobiome and the plant host, results from this wide range of coevolved relationships. We are just beginning to appreciate the many ways in which this complex and subtle coevolution acts in agricultural systems.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )