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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 03 Dec 2020 at 01:47 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 pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2020-12-02

Lupette J, E Maréchal (2020)

The Puzzling Conservation and Diversification of Lipid Droplets from Bacteria to Eukaryotes.

Results and problems in cell differentiation, 69:281-334.

Membrane compartments are amongst the most fascinating markers of cell evolution from prokaryotes to eukaryotes, some being conserved and the others having emerged via a series of primary and secondary endosymbiosis events. Membrane compartments comprise the system limiting cells (one or two membranes in bacteria, a unique plasma membrane in eukaryotes) and a variety of internal vesicular, subspherical, tubular, or reticulated organelles. In eukaryotes, the internal membranes comprise on the one hand the general endomembrane system, a dynamic network including organelles like the endoplasmic reticulum, the Golgi apparatus, the nuclear envelope, etc. and also the plasma membrane, which are linked via direct lateral connectivity (e.g. between the endoplasmic reticulum and the nuclear outer envelope membrane) or indirectly via vesicular trafficking. On the other hand, semi-autonomous organelles, i.e. mitochondria and chloroplasts, are disconnected from the endomembrane system and request vertical transmission following cell division. Membranes are organized as lipid bilayers in which proteins are embedded. The budding of some of these membranes, leading to the formation of the so-called lipid droplets (LDs) loaded with hydrophobic molecules, most notably triacylglycerol, is conserved in all clades. The evolution of eukaryotes is marked by the acquisition of mitochondria and simple plastids from Gram-positive bacteria by primary endosymbiosis events and the emergence of extremely complex plastids, collectively called secondary plastids, bounded by three to four membranes, following multiple and independent secondary endosymbiosis events. There is currently no consensus view of the evolution of LDs in the Tree of Life. Some features are conserved; others show a striking level of diversification. Here, we summarize the current knowledge on the architecture, dynamics, and multitude of functions of the lipid droplets in prokaryotes and in eukaryotes deriving from primary and secondary endosymbiosis events.

RevDate: 2020-12-02

Kaczanowski S (2020)

Symbiotic Origin of Apoptosis.

Results and problems in cell differentiation, 69:253-280.

The progress of evolutionary biology has revealed that symbiosis played a basic role in the evolution of complex eukaryotic organisms, including humans. Mitochondria are actually simplified endosymbiotic bacteria currently playing the role of cellular organelles. Mitochondrial domestication occurred at the very beginning of eukaryotic evolution. Mitochondria have two different basic functions: they produce energy using oxidative respiration, and they initiate different forms of apoptotic programmed/regulated cell death. Apoptotic programmed cell death may have different cytological forms. Mechanisms of apoptotic programmed cell death exist even in the unicellular organisms, and they play a basic role in the development of complex multicellular organisms, such as fungi, green plants, and animals. Multicellularity was independently established many times among eukaryotes. There are indications that apoptotic programmed cell death is a trait required for the establishment of multicellularity. Regulated cell death is initiated by many different parallel biochemical pathways. It is generally accepted that apoptosis evolved during mitochondrial domestication. However, there are different hypothetical models of the origin of apoptosis. The phylogenetic studies of my group indicate that apoptosis probably evolved during an evolutionary arms race between host ancestral eukaryotic predators and ancestral prey mitochondria (named protomitochondria). Protomitochondrial prey produced many different toxins as a defense against predators. From these toxins evolved extant apoptotic factors. There are indications that aerobic respiration and apoptosis co-evolved and are functionally linked in extant organisms. Perturbations of apoptosis and oxidative respiration are frequently observed during neoplastic transition. Our group showed that perturbations of apoptosis in yeasts also cause perturbations of oxidative respiration.

RevDate: 2020-11-25

Yu H, Haja DK, Schut GJ, et al (2020)

Structure of the respiratory MBS complex reveals iron-sulfur cluster catalyzed sulfane sulfur reduction in ancient life.

Nature communications, 11(1):5953 pii:10.1038/s41467-020-19697-7.

Modern day aerobic respiration in mitochondria involving complex I converts redox energy into chemical energy and likely evolved from a simple anaerobic system now represented by hydrogen gas-evolving hydrogenase (MBH) where protons are the terminal electron acceptor. Here we present the cryo-EM structure of an early ancestor in the evolution of complex I, the elemental sulfur (S0)-reducing reductase MBS. Three highly conserved protein loops linking cytoplasmic and membrane domains enable scalable energy conversion in all three complexes. MBS contains two proton pumps compared to one in MBH and likely conserves twice the energy. The structure also reveals evolutionary adaptations of MBH that enabled S0 reduction by MBS catalyzed by a site-differentiated iron-sulfur cluster without participation of protons or amino acid residues. This is the simplest mechanism proposed for reduction of inorganic or organic disulfides. It is of fundamental significance in the iron and sulfur-rich volcanic environments of early earth and possibly the origin of life. MBS provides a new perspective on the evolution of modern-day respiratory complexes and of catalysis by biological iron-sulfur clusters.

RevDate: 2020-11-24

Gao ZW, L Wang (2020)

[Progress in elucidating the origin of eukaryotes].

Yi chuan = Hereditas, 42(10):929-948.

Knowledge of the origin of eukaryotes is key to broadening our understanding of the eukaryotic genome and the relationship among internal structures within a eukaryotic cell. Since the discovery of archaea in 1977 and the proposal of three-domain tree of life by the American microbiologist Carl Woese, the intimate relationship in evolution between eukaryotes and archaea has been demonstrated by considerable experiments and analyses. From the beginning of the 21st century, with the development of phylogenetic methods and the discovery of new archaeal phyla more related to eukaryotes, increasing evidence has shown that Eukarya and Archaea should be merged into one domain, leading to a two-domain tree of life. Nowadays, the Asgard superphylum discovered via metagenomic analysis is regarded as the closest prokaryotes to eukaryotes. Nevertheless, several key questions are still under debate, such as what the ancestors of the eukaryotes were and when mitochondria emerged. Here, we review the current research progress regarding the changes of the tree of life and the detailed eukaryotic evolutionary mechanism. We show that the recent findings have greatly improved our knowledge on the origin of eukaryotes, which will pave the way for future studies.

RevDate: 2020-12-01

Agafonov VA, Negrobov VV, AU Igamberdiev (2020)

Symbiogenesis as a driving force of evolution: The legacy of Boris Kozo-Polyansky.

Bio Systems, 199:104302 pii:S0303-2647(20)30179-9 [Epub ahead of print].

We analyze evolutionary views of Boris Kozo-Polyansky (1890-1957) who was the first who formulated the symbiotic theory of evolution as a concept in his book, Symbiogenesis: A New Principle of Evolution (1924). Later, starting from 1967, Lynn Margulis independently formulated and further developed the concept of symbiogenesis. Although the ideas on the symbiotic origin of chloroplasts and mitochondria appeared earlier, the book of Kozo-Polyansky presented symbiogenesis as the main factor of complexification in the course of evolution, not only in relation to the origin of eukaryotic cell. Kozo-Polyansky incorporated the ideas of symbiogenesis into a broader paradigm that anticipated the important concepts of the modern Extended Evolutionary Synthesis such as the idea of net of life, the evolutionary role of apoptosis, the ideas of punctuated equilibrium, and the concept of metasystem transition.

RevDate: 2020-11-24

Khoshravesh R, Stata M, Adachi S, et al (2020)

Evolutionary Convergence of C4 Photosynthesis: A Case Study in the Nyctaginaceae.

Frontiers in plant science, 11:578739.

C4 photosynthesis evolved over 65 times, with around 24 origins in the eudicot order Caryophyllales. In the Caryophyllales family Nyctaginaceae, the C4 pathway is known in three genera of the tribe Nyctagineae: Allionia, Okenia and Boerhavia. Phylogenetically, Allionia and Boerhavia/Okenia are separated by three genera whose photosynthetic pathway is uncertain. To clarify the distribution of photosynthetic pathways in the Nyctaginaceae, we surveyed carbon isotope ratios of 159 species of the Nyctaginaceae, along with bundle sheath (BS) cell ultrastructure, leaf gas exchange, and C4 pathway biochemistry in five species from the two C4 clades and closely related C3 genera. All species in Allionia, Okenia and Boerhavia are C4, while no C4 species occur in any other genera of the family, including three that branch between Allionia and Boerhavia. This demonstrates that C4 photosynthesis evolved twice in Nyctaginaceae. Boerhavia species use the NADP-malic enzyme (NADP-ME) subtype of C4 photosynthesis, while Allionia species use the NAD-malic enzyme (NAD-ME) subtype. The BS cells of Allionia have many more mitochondria than the BS of Boerhavia. Bundle sheath mitochondria are closely associated with chloroplasts in Allionia which facilitates CO2 refixation following decarboxylation by mitochondrial NAD-ME. The close relationship between Allionia and Boerhavia could provide insights into why NADP-ME versus NAD-ME subtypes evolve, particularly when coupled to analysis of their respective genomes. As such, the group is an excellent system to dissect the organizational hierarchy of convergent versus divergent traits produced by C4 evolution, enabling us to understand when convergence is favored versus when divergent modifications can result in a common phenotype.

RevDate: 2020-11-22

Xu H, Zhou W, Zhan L, et al (2020)

The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats.

Aging, 12: pii:103894 [Epub ahead of print].

Chronic psychological stress (PS) cumulatively affects memory performance through the deleterious effects on hypothalamic-pituitary-adrenal axis regulation. Several functions damaged in cognitive impairment-related diseases are regulated by mitochondria-associated ER membranes (MAMs). To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the MAM proteome to improve PS-induced diabetes-associated cognitive decline (PSD), differentially expressed MAM proteins were identified among Zucker diabetic fatty rats, PSD rats, and PS combined with ZBPYR administration rats via iTRAQ with LC-MS/MS. Proteomic analysis revealed that the expressions of 85 and 33 proteins were altered by PS and ZBPYR treatment, respectively. Among these, 21 proteins were differentially expressed under both PS and ZBPYR treatments, whose functional categories included energy metabolism, lipid and protein metabolism, and synaptic dysfunction. Furthermore, calcium signaling and autophagy-related proteins may play roles in the pathogenesis of PSD and the mechanism of ZBPYR, respectively. Notably, KEGG pathway analysis suggested that 'Alzheimer's disease' and 'oxidative phosphorylation' pathways may be impaired in PSD pathogenesis, while ZBPYR could play a neuroprotective role through regulating the above pathways. Overall, exposure to chronic PS contributes to the evolution of diabetes-associated cognitive decline and ZBPYR might prevent and treat PSD by regulating the MAM proteome.

RevDate: 2020-11-20

Plese B, James Kenny N, Eleonora Rossi M, et al (2020)

Mitochondrial Evolution in the Demospongiae (Porifera): Phylogeny, Divergence Time, and Genome Biology.

Molecular phylogenetics and evolution pii:S1055-7903(20)30283-9 [Epub ahead of print].

The sponge class Demospongiae is the most speciose and morphologically diverse in the phylum Porifera, and the species within it are vital components of a range of ecosystems worldwide. Despite their ubiquity, a number of recalcitrant problems still remain to be solved regarding their phylogenetic inter-relationships, the timing of their appearance, and their mitochondrial biology, the latter of which is only beginning to be investigated. Here we generated 14 new demosponge mitochondrial genomes which, alongside previously published mitochondrial resources, were used to address these issues. In addition to phylogenomic analysis, we have used syntenic data and analysis of coding regions to forge a framework for understanding the inter-relationships between Demospongiae sub-classes and orders. We have also leveraged our new resources to study the mitochondrial biology of these clades in terms of codon usage, optimisation and gene expression, to understand how these vital cellular components may have contributed to the success of the Porifera. Our results strongly support a sister relationship between Keratosa and (Verongimorpha+Heteroscleromorpha), contradicting previous studies using nuclear markers. Our study includes one species of Clionaida, and show for the first time support for a grouping of Suberitida+(Clionaida+(Tethyida+Poecilosclerida). The findings of our phylogenetic analyses are supported by in-depth examination of structural and coding-level evidence from our mitochondrial data. A time-calibrated phylogeny estimated the origin of Demospongiae in the Cambrian (∼529 Mya), and suggest that most demosponge order crown-groups emerged in the Mesozoic. This work therefore provides a robust basis for considering demosponge phylogenetic relationships, as well as essential mitochondrial data for understanding the biological basis for their success and diversity.

RevDate: 2020-11-18

Lukeš J, Kaur B, D Speijer (2020)

RNA Editing in Mitochondria and Plastids: Weird and Widespread.

Trends in genetics : TIG pii:S0168-9525(20)30277-8 [Epub ahead of print].

Though widespread, RNA editing is rare, except in endosymbiotic organelles. A combination of higher mutation rates, relaxation of energetic constraints, and high genetic drift is found within plastids and mitochondria and is conducive for evolution and expansion of editing processes, possibly starting as repair mechanisms. To illustrate this, we present an exhaustive phylogenetic overview of editing types.

RevDate: 2020-11-18

Azim MF, TM Burch-Smith (2020)

Organelles-nucleus-plasmodesmata signaling (ONPS): an update on its roles in plant physiology, metabolism and stress responses.

Current opinion in plant biology, 58:48-59 pii:S1369-5266(20)30111-4 [Epub ahead of print].

Plasmodesmata allow movement of metabolites and signaling molecules between plant cells and are, therefore, critical players in plant development and physiology, and in responding to environmental signals and stresses. There is emerging evidence that plasmodesmata are controlled by signaling originating from other organelles, primarily the chloroplasts and mitochondria. These signals act in the nucleus to alter expression of genetic pathways that control both trafficking via plasmodesmata and the plasmodesmatal pores themselves. This control circuit was dubbed organelle-nucleus-plasmodesmata signaling (ONPS). Here we discuss how ONPS arose during plant evolution and highlight the discovery of an ONPS-like module for regulating stomata. We also consider recent findings that illuminate details of the ONPS circuit and its roles in plant physiology, metabolism, and defense.

RevDate: 2020-11-15

Dhorne-Pollet S, Barrey E, N Pollet (2020)

A new method for long-read sequencing of animal mitochondrial genomes: application to the identification of equine mitochondrial DNA variants.

BMC genomics, 21(1):785.

BACKGROUND: Mitochondrial DNA is remarkably polymorphic. This is why animal geneticists survey mitochondrial genomes variations for fundamental and applied purposes. We present here an approach to sequence whole mitochondrial genomes using nanopore long-read sequencing. Our method relies on the selective elimination of nuclear DNA using an exonuclease treatment and on the amplification of circular mitochondrial DNA using a multiple displacement amplification step.

RESULTS: We optimized each preparative step to obtain a 100 million-fold enrichment of horse mitochondrial DNA relative to nuclear DNA. We sequenced these amplified mitochondrial DNA using nanopore sequencing technology and obtained mitochondrial DNA reads that represented up to half of the sequencing output. The sequence reads were 2.3 kb of mean length and provided an even coverage of the mitochondrial genome. Long-reads spanning half or more of the whole mtDNA provided a coverage that varied between 118X and 488X. We evaluated SNPs identified using these long-reads by Sanger sequencing as ground truth and found a precision of 100.0%; a recall of 93.1% and a F1-score of 0.964 using the Twilight horse mtDNA reference. The choice of the mtDNA reference impacted variant calling efficiency with F1-scores varying between 0.947 and 0.964.

CONCLUSIONS: Our method to amplify mtDNA and to sequence it using the nanopore technology is usable for mitochondrial DNA variant analysis. With minor modifications, this approach could easily be applied to other large circular DNA molecules.

RevDate: 2020-12-01

Hirase S, Tezuka A, Nagano AJ, et al (2020)

Integrative genomic phylogeography reveals signs of mitonuclear incompatibility in a natural hybrid goby population.

Evolution; international journal of organic evolution [Epub ahead of print].

Hybridization between divergent lineages generates new allelic combinations. One mechanism that can hinder the formation of hybrid populations is mitonuclear incompatibility, that is, dysfunctional interactions between proteins encoded in the nuclear and mitochondrial genomes (mitogenomes) of diverged lineages. Theoretically, selective pressure due to mitonuclear incompatibility can affect genotypes in a hybrid population in which nuclear genomes and mitogenomes from divergent lineages admix. To directly and thoroughly observe this key process, we de novo sequenced the 747-Mb genome of the coastal goby, Chaenogobius annularis, and investigated its integrative genomic phylogeographics using RNA-sequencing, RAD-sequencing, genome resequencing, whole mitogenome sequencing, amplicon sequencing, and small RNA-sequencing. Chaenogobius annularis populations have been geographically separated into Pacific Ocean (PO) and Sea of Japan (SJ) lineages by past isolation events around the Japanese archipelago. Despite the divergence history and potential mitonuclear incompatibility between these lineages, the mitogenomes of the PO and SJ lineages have coexisted for generations in a hybrid population on the Sanriku Coast. Our analyses revealed accumulation of nonsynonymous substitutions in the PO-lineage mitogenomes, including two convergent substitutions, as well as signals of mitochondrial lineage-specific selection on mitochondria-related nuclear genes. Finally, our data implied that a microRNA gene was involved in resolving mitonuclear incompatibility. Our integrative genomic phylogeographic approach revealed that mitonuclear incompatibility can affect genome evolution in a natural hybrid population.

RevDate: 2020-11-18

Lin ZJ, Wang X, Wang J, et al (2020)

Comparative analysis reveals the expansion of mitochondrial DNA control region containing unusually high G-C tandem repeat arrays in Nasonia vitripennis.

International journal of biological macromolecules pii:S0141-8130(20)34933-3 [Epub ahead of print].

Insect mitochondrial DNA (mtDNA) ranges from 14 to 19 kbp, and the size difference is attributed to the AT-rich control region. Jewel wasps have a parasitoid lifestyle, which may affect mitochondria function and evolution. We sequenced, assembled, and annotated mitochondrial genomes in Nasonia and outgroup species. Gene composition and order are conserved within Nasonia, but they differ from other parasitoids by two large inversion events that were not reported before. We observed a much higher substitution rate relative to the nuclear genome and mitochondrial introgression between N. giraulti and N. oneida, which is consistent with previous studies. Most strikingly, N. vitripennis mtDNA has an extremely long control region (7665 bp), containing twenty-nine 217 bp tandem repeats and can fold into a super-cruciform structure. In contrast to tandem repeats commonly found in other mitochondria, these high-copy repeats are highly conserved (98.7% sequence identity), much longer in length (approximately 8 Kb), extremely GC-rich (50.7%), and CpG-rich (percent CpG 19.4% vs. 1.1% in coding region), resulting in a 23 kbp mtDNA beyond the typical size range in insects. These N. vitripennis-specific mitochondrial repeats are not related to any known sequences in insect mitochondria. Their evolutionary origin and functional consequences warrant further investigations.

RevDate: 2020-11-17

Pearson SA, JA Cowan (2020)

Evolution of the human mitochondrial ABCB7 [2Fe-2S](GS)4 cluster exporter and the molecular mechanism of an E433K disease-causing mutation.

Archives of biochemistry and biophysics pii:S0003-9861(20)30670-6 [Epub ahead of print].

Iron-sulfur cluster proteins play key roles in a multitude of cellular processes. Iron-sulfur cofactors are assembled primarily in mitochondria and are then exported to the cytosol by use of an ABCB7 transporter. It has been shown that the yeast mitochondrial transporter Atm1 can export glutathione-coordinated iron-sulfur clusters, [2Fe-2S](SG)4, providing a source of cluster units for cytosolic iron-sulfur cluster assembly systems. This pathway is consistent with the endosymbiotic model of mitochondrial evolution where homologous bacterial heavy metal transporters, utilizing metal glutathione adducts, were adapted for use in eukaryotic mitochondria. Herein, the basis for endosymbiotic evolution of the human cluster export protein (ABCB7) is developed through a BLAST analysis of transporters from ancient proteobacteria. In addition, a functional comparison of native human protein, versus a disease-causing mutant, demonstrates a key role for residue E433 in promoting cluster transport. Dysfunction in mitochondrial export of Fe-S clusters is a likely cause of the disease condition X-linked sideroblastic anemia.

RevDate: 2020-11-06

Tort F, Barredo E, Parthasarathy R, et al (2020)

Biallelic mutations in NDUFA8 cause complex I deficiency in two siblings with favorable clinical evolution.

Molecular genetics and metabolism pii:S1096-7192(20)30205-5 [Epub ahead of print].

Isolated complex I (CI) deficiency is the most common cause of oxidative phosphorylation (OXPHOS) dysfunction. Whole-exome sequencing identified biallelic mutations in NDUFA8 (c.[293G > T]; [293G > T], encoding for an accessory subunit of CI, in two siblings with a favorable clinical evolution. The individuals reported here are practically asymptomatic, with the exception of slight failure to thrive and some language difficulties at the age of 6 and 9 years, respectively. These observations are remarkable since the vast majority of patients with CI deficiency, including the only NDUFA8 patient reported so far, showed an extremely poor clinical outcome. Western blot studies demonstrated that NDUFA8 protein was strongly reduced in the patients' fibroblasts and muscle extracts. In addition, there was a marked and specific decrease in the steady-state levels of CI subunits. BN-PAGE demonstrated an isolated defect in the assembly and the activity of CI with impaired supercomplexes formation and abnormal accumulation of CI subassemblies. Confocal microscopy analysis in fibroblasts showed rounder mitochondria and diminished branching degree of the mitochondrial network. Functional complementation studies demonstrated disease-causality for the identified mutation as lentiviral transduction with wild-type NDUFA8 cDNA restored the steady-state levels of CI subunits and completely recovered the deficient enzymatic activity in immortalized mutant fibroblasts. In summary, we provide additional evidence of the involvement of NDUFA8 as a mitochondrial disease-causing gene associated with altered mitochondrial morphology, CI deficiency, impaired supercomplexes formation, and very mild progression of the disease.

RevDate: 2020-11-28

Penna E, Pizzella A, Cimmino F, et al (2020)

Neurodevelopmental Disorders: Effect of High-Fat Diet on Synaptic Plasticity and Mitochondrial Functions.

Brain sciences, 10(11):.

Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people's lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30-50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.

RevDate: 2020-11-13

Fukuda T, Ebi Y, Saigusa T, et al (2020)

Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast.

eLife, 9:.

Degradation of mitochondria through mitophagy contributes to the maintenance of mitochondrial function. In this study, we identified that Atg43, a mitochondrial outer membrane protein, serves as a mitophagy receptor in the model organism Schizosaccharomyces pombe to promote the selective degradation of mitochondria. Atg43 contains an Atg8-family-interacting motif essential for mitophagy. Forced recruitment of Atg8 to mitochondria restores mitophagy in Atg43-deficient cells, suggesting that Atg43 tethers expanding isolation membranes to mitochondria. We found that the mitochondrial import factors, including the Mim1-Mim2 complex and Tom70, are crucial for mitophagy. Artificial mitochondrial loading of Atg43 bypasses the requirement of the import factors, suggesting that they contribute to mitophagy through Atg43. Atg43 not only maintains growth ability during starvation but also facilitates vegetative growth through its mitophagy-independent function. Thus, Atg43 is a useful model to study the mechanism and physiological roles, as well as the origin and evolution, of mitophagy in eukaryotes.

RevDate: 2020-12-01

Ryan DG, Frezza C, LA O'Neill (2020)

TCA cycle signalling and the evolution of eukaryotes.

Current opinion in biotechnology, 68:72-88 pii:S0958-1669(20)30144-0 [Epub ahead of print].

A major question remaining in the field of evolutionary biology is how prokaryotic organisms made the leap to complex eukaryotic life. The prevailing theory depicts the origin of eukaryotic cell complexity as emerging from the symbiosis between an α-proteobacterium, the ancestor of present-day mitochondria, and an archaeal host (endosymbiont theory). A primary contribution of mitochondria to eukaryogenesis has been attributed to the mitochondrial genome, which enabled the successful internalisation of bioenergetic membranes and facilitated remarkable genome expansion. It has also been postulated that a key contribution of the archaeal host during eukaryogenesis was in providing 'archaeal histones' that would enable compaction and regulation of an expanded genome. Yet, how the communication between the host and the symbiont evolved is unclear. Here, we propose an evolutionary concept in which mitochondrial TCA cycle signalling was also a crucial player during eukaryogenesis enabling the dynamic control of an expanded genome via regulation of DNA and histone modifications. Furthermore, we discuss how TCA cycle remodelling is a common evolutionary strategy invoked by eukaryotic organisms to coordinate stress responses and gene expression programmes, with a particular focus on the TCA cycle-derived metabolite itaconate.

RevDate: 2020-10-30

Wang ZJ, Chen GJ, Zhang GJ, et al (2020)

Dynamic evolution of transposable elements, demographic history, and gene content of paleognathous birds.

Zoological research [Epub ahead of print].

Palaeognathae includes ratite and tinamou species that are important for understanding early avian evolution. Here, we analyzed the whole-genome sequences of 15 paleognathous species to infer their demographic histories, which are presently unknown. We found that most species showed a reduction of population size since the beginning of the last glacial period, except for those species distributed in Australasia and in the far south of South America. Different degrees of contraction and expansion of transposable elements (TE) have shaped the paleognathous genome architecture, with a higher transposon removal rate in tinamous than in ratites. One repeat family, AviRTE, likely underwent horizontal transfer from tropical parasites to the ancestor of little and undulated tinamous about 30 million years ago. Our analysis of gene families identified rapid turnover of immune and reproduction-related genes but found no evidence of gene family changes underlying the convergent evolution of flightlessness among ratites. We also found that mitochondrial genes have experienced a faster evolutionary rate in tinamous than in ratites, with the former also showing more degenerated W chromosomes. This result can be explained by the Hill-Robertson interference affecting genetically linked W chromosomes and mitochondria. Overall, we reconstructed the evolutionary history of the Palaeognathae populations, genes, and TEs. Our findings of co-evolution between mitochondria and W chromosomes highlight the key difference in genome evolution between species with ZW sex chromosomes and those with XY sex chromosomes.

RevDate: 2020-12-01

Hartmann FE, Duhamel M, Carpentier F, et al (2020)

Recombination suppression and evolutionary strata around mating-type loci in fungi: documenting patterns and understanding evolutionary and mechanistic causes.

The New phytologist [Epub ahead of print].

Genomic regions determining sexual compatibility often display recombination suppression, as occurs in sex chromosomes, plant self-incompatibility loci and fungal mating-type loci. Regions lacking recombination can extend beyond the genes determining sexes or mating types, by several successive steps of recombination suppression. Here we review the evidence for recombination suppression around mating-type loci in fungi, sometimes encompassing vast regions of the mating-type chromosomes. The suppression of recombination at mating-type loci in fungi has long been recognized and maintains the multiallelic combinations required for correct compatibility determination. We review more recent evidence for expansions of recombination suppression beyond mating-type genes in fungi ('evolutionary strata'), which have been little studied and may be more pervasive than commonly thought. We discuss testable hypotheses for the ultimate (evolutionary) and proximate (mechanistic) causes for such expansions of recombination suppression, including (1) antagonistic selection, (2) association of additional functions to mating-type, such as uniparental mitochondria inheritance, (3) accumulation in the margin of nonrecombining regions of various factors, including deleterious mutations or transposable elements resulting from relaxed selection, or neutral rearrangements resulting from genetic drift. The study of recombination suppression in fungi could thus contribute to our understanding of recombination suppression expansion across a broader range of organisms.

RevDate: 2020-10-27

Vosseberg J, van Hooff JJE, Marcet-Houben M, et al (2020)

Timing the origin of eukaryotic cellular complexity with ancient duplications.

Nature ecology & evolution pii:10.1038/s41559-020-01320-z [Epub ahead of print].

Eukaryogenesis is one of the most enigmatic evolutionary transitions, during which simple prokaryotic cells gave rise to complex eukaryotic cells. While evolutionary intermediates are lacking, gene duplications provide information on the order of events by which eukaryotes originated. Here we use a phylogenomics approach to reconstruct successive steps during eukaryogenesis. We find that gene duplications roughly doubled the proto-eukaryotic gene repertoire, with families inherited from the Asgard archaea-related host being duplicated most. By relatively timing events using phylogenetic distances, we inferred that duplications in cytoskeletal and membrane-trafficking families were among the earliest events, whereas most other families expanded predominantly after mitochondrial endosymbiosis. Altogether, we infer that the host that engulfed the proto-mitochondrion had some eukaryote-like complexity, which drastically increased upon mitochondrial acquisition. This scenario bridges the signs of complexity observed in Asgard archaeal genomes to the proposed role of mitochondria in triggering eukaryogenesis.

RevDate: 2020-11-03

Qu C, Wang L, Zhao Y, et al (2020)

Molecular Evolution of Maize Ascorbate Peroxidase Genes and Their Functional Divergence.

Genes, 11(10):.

Ascorbate peroxidase (APX) is an important antioxidant enzyme. APXs in maize are encoded by multiple genes and exist as isoenzymes. The evolutionary history and functional divergence of the maize APX gene family were analyzed through comparative genomic and experimental data on the Internet in this paper. APX genes in higher plants were divided into classes A, B, and C. Each type of APX gene in angiosperms only had one ancestral gene that was duplicated along with the genome duplication or local (or tandem) duplication of the angiosperm. A total of eight genes were retained in maize and named APXa1, APXa2, APXa3, APXb1, APXb2, APXc1.1, APXc1.2, and APXc2. The APX genes of class A were located in the chloroplasts or mitochondria, and the class B and C genes were localized in the peroxisomes and cytoplasm, respectively. The expression patterns of eight APXs were different in vegetative and reproductive organs at different growth and development stages. APXa1 and APXb1 of maize may participate in the antioxidant metabolism of vegetative organs under normal conditions. APXa2, APXb2, APXc1.1, and APXc1.2 may be involved in the stress response, and APXb2 and APXc2 may participate in the senescence response. These results provide a basis for cultivating high-yield and resistant maize varieties.

RevDate: 2020-11-17

Kang JS, Zhang HR, Wang YR, et al (2020)

Distinctive evolutionary pattern of organelle genomes linked to the nuclear genome in Selaginellaceae.

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

Plastids and mitochondria are endosymbiotic organelles that store genetic information. The genomes of these organelles generally exhibit contrasting patterns regarding genome architecture and genetic content. However, they have similar genetic features in Selaginellaceae, and little is known about what causes parallel evolution. Here, we document the multipartite plastid genomes (plastomes) and the highly divergent mitochondrial genomes (mitogenomes) from spikemoss obtained by combining short- and long-reads. The 188-kb multipartite plastome has three ribosomal operon copies in the master genomic conformation, creating the alternative subgenomic conformation composed of 110- and 78-kb subgenomes. The long-read data indicated that the two different genomic conformations were present in almost equal proportions in the plastomes of Selaginella nipponica. The mitogenome of S. nipponica was assembled into 27 contigs with a total size of 110 kb. All contigs contained directly arranged repeats at both ends, which introduced multiple conformations. Our results showed that plastomes and mitogenomes share high tRNA losses, GC-biased nucleotides, elevated substitution rates and complicated organization. The exploration of nuclear-encoded organelle DNA replication, recombination and repair proteins indicated that, several single-targeted proteins, particularly plastid-targeted recombinase A1, have been lost in Selaginellaceae; conversely, the dual-targeted proteins remain intact. According to the reported function of recombinase A1, we propose that the plastomes of spikemoss often fail to pair homologous sequences during recombination, and the dual-targeted proteins play a key role in the convergent genetic features of plastomes and mitogenomes. Our results provide a distinctive evolutionary pattern of the organelle genomes in Selaginellaceae and evidence of their convergent evolution.

RevDate: 2020-10-20

Teulière J, Bernard G, E Bapteste (2020)

The Distribution of Genes Associated With Regulated Cell Death Is Decoupled From the Mitochondrial Phenotypes Within Unicellular Eukaryotic Hosts.

Frontiers in cell and developmental biology, 8:536389.

Genetically regulated cell death (RCD) occurs in all domains of life. In eukaryotes, the evolutionary origin of the mitochondrion and of certain forms of RCD, in particular apoptosis, are thought to coincide, suggesting a central general role for mitochondria in cellular suicide. We tested this mitochondrial centrality hypothesis across a dataset of 67 species of protists, presenting 5 classes of mitochondrial phenotypes, including functional mitochondria, metabolically diversified mitochondria, functionally reduced mitochondria (Mitochondrion Related Organelle or MRO) and even complete absence of mitochondria. We investigated the distribution of genes associated with various forms of RCD. No homologs for described mammalian regulators of regulated necrosis could be identified in our set of 67 unicellular taxa. Protists with MRO and the secondarily a mitochondriate Monocercomonoides exilis display heterogeneous reductions of apoptosis gene sets with respect to typical mitochondriate protists. Remarkably, despite the total lack of mitochondria in M. exilis, apoptosis-associated genes could still be identified. These same species of protists with MRO and M. exilis harbored non-reduced autophagic cell death gene sets. Moreover, transiently multicellular protist taxa appeared enriched in apoptotic and autophagy associated genes compared to free-living protists. This analysis suggests that genes associated with apoptosis in animals and the presence of the mitochondria are significant yet non-essential biological components for RCD in protists. More generally, our results support the hypothesis of a selection for RCD, including both apoptosis and autophagy, as a developmental mechanism linked to multicellularity.

RevDate: 2020-11-21

Friesen CR, Noble DWA, M Olsson (2020)

The role of oxidative stress in postcopulatory selection.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 375(1813):20200065.

Two decades ago, von Schantz et al. (von Schantz T, Bensch S, Grahn M, Hasselquist D, Wittzell H. 1999 Good genes, oxidative stress and condition-dependent sexual signals. Proc. R. Soc. B 266, 1-12. (doi:10.1098/rspb.1999.0597)) united oxidative stress (OS) biology with sexual selection and life-history theory. This set the scene for analysis of how evolutionary trade-offs may be mediated by the increase in reactive molecules resulting from metabolic processes at reproduction. Despite 30 years of research on OS effects on infertility in humans, one research area that has been left behind in this integration of evolution and OS biology is postcopulatory sexual selection-this integration is long overdue. We review the basic mechanisms in OS biology, why mitochondria are the primary source of ROS and ATP production during oxidative metabolism, and why sperm, and its performance, is uniquely susceptible to OS. We also review how postcopulatory processes select for antioxidation in seminal fluids to counter OS and the implications of the net outcome of these processes on sperm damage, sperm storage, and female and oocyte manipulation of sperm metabolism and repair of DNA to enhance offspring fitness. This article is part of the theme issue 'Fifty years of sperm competition'.

RevDate: 2020-10-31

Lima-Posada I, NA Bobadilla (2020)

Understanding the opposite effects of sex hormones in mediating renal injury.

Nephrology (Carlton, Vic.) [Epub ahead of print].

According to epidemiological studies, chronic kidney disease (CKD) affects more women than men, but the incidence of end-stage renal disease is higher in men than in women. However, most of these studies have not considered the incidence of CKD in women of reproductive or post-menopausal age, and even fewer with hormone replacement therapy. Some meta-analyses have reported an exacerbated progression of CKD in men compared with women. Consequently, in most of the experimental models of renal injury, men of reproductive age exhibit more abnormalities in renal function and structure that lead to greater progression to CKD than women, which suggests that these differences are mediated by sex hormones rather than by other factors. This review intends to show the mechanisms regulated by oestrogen or testosterone that may explain the different risks and evolution of renal diseases between men and women. Regardless of the initial cause of kidney disease, sex hormones have been implicated in modulating vascular tone, oxidative stress, inflammation and apoptosis. Finally, our previous study highlights the mechanisms by which the transition from acute kidney injury to CKD does not occur in female rats as commonly as it does in male rats. This review not only identifies sex differences in several kidney diseases but also supports potential therapeutic opportunities to reduce or prevent the progression of CKD and highlights the importance of considering sex differences in the design of any clinical study.

RevDate: 2020-11-02
CmpDate: 2020-11-02

Brady SW, Liu Y, Ma X, et al (2020)

Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations.

Nature communications, 11(1):5183.

Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuroblastoma samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years. COSMIC mutational signature 18, previously associated with reactive oxygen species, is the most common cause of driver point mutations in neuroblastoma, including most ALK and Ras-activating variants. Signature 18 appears early and is continuous throughout disease evolution. Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.

RevDate: 2020-10-21
CmpDate: 2020-10-21

GÓmez-Zurita J, Platania L, A Cardoso (2020)

A new species of the genus Tricholapita nom. nov. and stat. nov. (Coleoptera: Chrysomelidae, Eumolpinae) from New Caledonia.

Zootaxa, 4858(1):zootaxa.4858.1.5 pii:zootaxa.4858.1.5.

Tricholapita Gómez-Zurita and Cardoso nom. nov. is proposed as the replacement name for the leaf beetle taxon Lapita Gómez-Zurita and Cardoso, 2014, nec Bickel, 2002. Moreover, the rank of Tricholapita stat. nov. is elevated from subgenus of Taophila Heller, 1916 to generic status. Phylogenetic evidence based on mtDNA rrnS sequences and diagnostic morphological characters reveals a new species from the south of Grande Terre in New Caledonia, which is described: Tricholapita reidi sp. nov.

RevDate: 2020-10-13

da Veiga Moreira J, Schwartz L, M Jolicoeur (2020)

Targeting Mitochondrial Singlet Oxygen Dynamics Offers New Perspectives for Effective Metabolic Therapies of Cancer.

Frontiers in oncology, 10:573399.

The occurrence of mitochondrial respiration has allowed evolution toward more complex and advanced life forms. However, its dysfunction is now also seen as the most probable cause of one of the biggest scourges in human health, cancer. Conventional cancer treatments such as chemotherapy, which mainly focus on disrupting the cell division process, have shown being effective in the attenuation of various cancers but also showing significant limits as well as serious sides effects. Indeed, the idea that cancer is a metabolic disease with mitochondria as the central site of the pathology is now emerging, and we provide here a review supporting this "novel" hypothesis re-actualizing past century Otto Warburg's thoughts. Our conclusion, while integrating literature, is that mitochondrial activity and, in particular, the activity of cytochrome c oxidase, complex IV of the ETC, plays a fundamental role in the effectiveness or non-effectiveness of chemotherapy, immunotherapy and probably radiotherapy treatments. We therefore propose that cancer cells mitochondrial singlet oxygen (1O2) dynamics may be an efficient target for metabolic therapy development.

RevDate: 2020-10-07

Bolmatov D, Carrillo JY, Sumpter BG, et al (2020)

Double membrane formation in heterogeneous vesicles.

Soft matter, 16(38):8806-8817.

Lipids are capable of forming a variety of structures, including multi-lamellar vesicles. Layered lipid membranes are found in cell organelles, such as autophagosomes and mitochondria. Here, we present a mechanism for the formation of a double-walled vesicle (i.e., two lipid bilayers) from a unilamellar vesicle through the partitioning and phase separation of a small molecule. Using molecular dynamics simulations, we show that double membrane formation proceeds via a nucleation and growth process - i.e., after a critical concentration of the small molecules, a patch of double membrane nucleates and grows to cover the entire vesicle. We discuss the implications of this mechanism and theoretical approaches for understanding the evolution and formation of double membranes.

RevDate: 2020-11-23

Mayr SJ, Mendel RR, G Schwarz (2021)

Molybdenum cofactor biology, evolution and deficiency.

Biochimica et biophysica acta. Molecular cell research, 1868(1):118883.

The molybdenum cofactor (Moco) represents an ancient metal‑sulfur cofactor, which participates as catalyst in carbon, nitrogen and sulfur cycles, both on individual and global scale. Given the diversity of biological processes dependent on Moco and their evolutionary age, Moco is traced back to the last universal common ancestor (LUCA), while Moco biosynthetic genes underwent significant changes through evolution and acquired additional functions. In this review, focused on eukaryotic Moco biology, we elucidate the benefits of gene fusions on Moco biosynthesis and beyond. While originally the gene fusions were driven by biosynthetic advantages such as coordinated expression of functionally related proteins and product/substrate channeling, they also served as origin for the development of novel functions. Today, Moco biosynthetic genes are involved in a multitude of cellular processes and loss of the according gene products result in severe disorders, both related to Moco biosynthesis and secondary enzyme functions.

RevDate: 2020-11-23

Braymer JJ, Freibert SA, Rakwalska-Bange M, et al (2021)

Mechanistic concepts of iron-sulfur protein biogenesis in Biology.

Biochimica et biophysica acta. Molecular cell research, 1868(1):118863.

Iron-sulfur (Fe/S) proteins are present in virtually all living organisms and are involved in numerous cellular processes such as respiration, photosynthesis, metabolic reactions, nitrogen fixation, radical biochemistry, protein synthesis, antiviral defense, and genome maintenance. Their versatile functions may go back to the proposed role of their Fe/S cofactors in the origin of life as efficient catalysts and electron carriers. More than two decades ago, it was discovered that the in vivo synthesis of cellular Fe/S clusters and their integration into polypeptide chains requires assistance by complex proteinaceous machineries, despite the fact that Fe/S proteins can be assembled chemically in vitro. In prokaryotes, three Fe/S protein biogenesis systems are known; ISC, SUF, and the more specialized NIF. The former two systems have been transferred by endosymbiosis from bacteria to mitochondria and plastids, respectively, of eukaryotes. In their cytosol, eukaryotes use the CIA machinery for the biogenesis of cytosolic and nuclear Fe/S proteins. Despite the structural diversity of the protein constituents of these four machineries, general mechanistic concepts underlie the complex process of Fe/S protein biogenesis. This review provides a comprehensive and comparative overview of the various known biogenesis systems in Biology, and summarizes their common or diverging molecular mechanisms, thereby illustrating both the conservation and diverse adaptions of these four machineries during evolution and under different lifestyles. Knowledge of these fundamental biochemical pathways is not only of basic scientific interest, but is important for the understanding of human 'Fe/S diseases' and can be used in biotechnology.

RevDate: 2020-11-20

Friedl J, Knopp MR, Groh C, et al (2020)

More than just a ticket canceller: the mitochondrial processing peptidase tailors complex precursor proteins at internal cleavage sites.

Molecular biology of the cell, 31(24):2657-2668.

Most mitochondrial proteins are synthesized as precursors that carry N-terminal presequences. After they are imported into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase (MPP). Using the mitochondrial tandem protein Arg5,6 as a model substrate, we demonstrate that MPP has an additional role in preprotein maturation, beyond the removal of presequences. Arg5,6 is synthesized as a polyprotein precursor that is imported into mitochondria and subsequently separated into two distinct enzymes. This internal processing is performed by MPP, which cleaves the Arg5,6 precursor at its N-terminus and at an internal site. The peculiar organization of Arg5,6 is conserved across fungi and reflects the polycistronic arginine operon in prokaryotes. MPP cleavage sites are also present in other mitochondrial fusion proteins from fungi, plants, and animals. Hence, besides its role as a "ticket canceller" for removal of presequences, MPP exhibits a second conserved activity as an internal processing peptidase for complex mitochondrial precursor proteins.

RevDate: 2020-10-29
CmpDate: 2020-10-22

Tan DX, R Hardeland (2020)

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19.

Molecules (Basel, Switzerland), 25(19):.

Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host's tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.

RevDate: 2020-11-17

Cheong A, Lingutla R, J Mager (2020)

Expression analysis of mammalian mitochondrial ribosomal protein genes.

Gene expression patterns : GEP, 38:119147 pii:S1567-133X(20)30170-8 [Epub ahead of print].

Mitochondrial ribosomal proteins (MRPs) are essential components for the structural and functional integrity of the mitoribosome complex. Throughout evolution, the mammalian mitoribosome has acquired new Mrp genes to compensate for loss of ribosomal RNA. More than 80 MRPs have been identified in mammals. Here we document expression pattern of 79 Mrp genes during mouse development and adult tissues and find that these genes are consistently expressed throughout early embryogenesis with little stage or tissue specificity. Further investigation of the amino acid sequence reveals that this group of proteins has little to no protein similarity. Recent work has shown that the majority of Mrp genes are essential resulting in early embryonic lethality, suggesting no functional redundancy among the group. Taken together, these results indicate that the Mrp genes are not a gene family descended from a single ancestral gene, and that each MRP has unique and essential role in the mitoribosome complex. The lack of functional redundancy is surprising given the importance of the mitoribosome for cellular and organismal viability. Further, these data suggest that genomic variants in Mrp genes may be causative for early pregnancy loss and should be evaluated as clinically.

RevDate: 2020-10-23
CmpDate: 2020-10-23

Silva de Souza S, Machado RN, Custódio da Costa J, et al (2020)

Severe damages caused by Malathion exposure in Colossoma macropomum.

Ecotoxicology and environmental safety, 205:111340.

The increase in pesticide use in response to agricultural demands poses a risk to non-target organisms, including fish. Integrated analysis of biochemical, histopathological and genetic parameters in fish exposed to Malathion insecticide provide information on the toxicity mechanisms of this pesticide, which is classified as a probable carcinogen for humans. The present study assessed the biological responses of Colossoma macropomum after exposure to Malathion. We started determining the lethal concentration, which is the concentration capable of killing 50% of the subjects in an acute toxicity test (LC50-96 h), which was 15.77 ± 3.30 mgL-1. The fish were, then, exposed to Malathion during 96 h at a sublethal concentration, 7.30 mgL-1. Overall, we observed an increased activity of biotransformation and antioxidant enzymes, which reduced production of mitochondrial reactive oxygen species after 96 h exposure, as well as kept constant the mitochondrial respiration, Acetylcholinesterase activity and DNA damage. However, fish exposed to insecticide presented severe gill histopathological damage and increased expression of proto-oncogene ras. Taken together, the results suggest that, after four days of exposure to the Malathion, C. macropomum efficiently activates its defense mechanisms, suggesting that the basal response mechanisms are responsive. On the other hand, histopathologic damages evidenced the adverse effects of Malathion on fish, since it promoted gill necrosis and increased the expression of ras oncogene that is directly related to tumorigenesis events.

RevDate: 2020-10-08
CmpDate: 2020-10-08

Camus MF (2020)

The perils of cheating.

eLife, 9:.

Experiments on mitochondrial DNA in worms highlight that cheating does not always pay off.

RevDate: 2020-11-03

Yamada Y, Sato Y, Nakamura T, et al (2020)

Evolution of drug delivery system from viewpoint of controlled intracellular trafficking and selective tissue targeting toward future nanomedicine.

Journal of controlled release : official journal of the Controlled Release Society, 327:533-545.

Due to the rapid changes that have occurred in the field of drug discovery and the recent developments in the early 21st century, the role of drug delivery systems (DDS) has become increasingly more important. For the past 20 years, our laboratory has been developing gene delivery systems based on lipid-based delivery systems. One of our efforts has been directed toward developing a multifunctional envelope-type nano device (MEND) by modifying the particle surface with octaarginine, which resulted in a remarkably enhanced cellular uptake and improved intracellular trafficking of plasmid DNA (pDNA). When we moved to in vivo applications, however, we were faced with the PEG-dilemma and we shifted our strategy to the incorporation of ionizable cationic lipids into our system. This resulted in some dramatic improvements over our original design and this can be attributed to the development of a new lipid library. We have also developed a mitochondrial targeting system based on a membrane fusion mechanism using a MITO-Porter, which can deliver nucleic acids/pDNA into the matrix of mitochondria. After the appearance of antibody medicines, Opdivo, an immune checkpoint inhibitor, has established cancer immunology as the 4th strategy in cancer therapy. Our DDS technologies can also be applied to this new field of cancer therapy to cure cancer by controlling our immune mechanisms. The latest studies are summarized in this review article.

RevDate: 2020-09-28

Mallard J, Hucteau E, Schott R, et al (2020)

Evolution of Physical Status From Diagnosis to the End of First-Line Treatment in Breast, Lung, and Colorectal Cancer Patients: The PROTECT-01 Cohort Study Protocol.

Frontiers in oncology, 10:1304.

Background: Cancer cachexia and exacerbated fatigue represent two hallmarks in cancer patients, negatively impacting their exercise tolerance and ultimately their quality of life. However, the characterization of patients' physical status and exercise tolerance and, most importantly, their evolution throughout cancer treatment may represent the first step in efficiently counteracting their development with prescribed and tailored exercise training. In this context, the aim of the PROTECT-01 study will be to investigate the evolution of physical status, from diagnosis to the end of first-line treatment, of patients with one of the three most common cancers (i.e., lung, breast, and colorectal). Methods: The PROTECT-01 cohort study will include 300 patients equally divided between lung, breast and colorectal cancer. Patients will perform a series of assessments at three visits throughout the treatment: (1) between the date of diagnosis and the start of treatment, (2) 8 weeks after the start of treatment, and (3) after the completion of first-line treatment or at the 6-months mark, whichever occurs first. For each of the three visits, subjective and objective fatigue, maximal voluntary force, body composition, cachexia, physical activity level, quality of life, respiratory function, overall physical performance, and exercise tolerance will be assessed. Discussion: The present study is aimed at identifying the nature and severity of maladaptation related to exercise intolerance in the three most common cancers. Therefore, our results should contribute to the delineation of the needs of each group of patients and to the determination of the most valuable exercise interventions in order to counteract these maladaptations. This descriptive and comprehensive approach is a prerequisite in order to elaborate, through future interventional research projects, tailored exercise strategies to counteract specific symptoms that are potentially cancer type-dependent and, in fine, to improve the health and quality of life of cancer patients. Moreover, our concomitant focus on fatigue and cachexia will provide insightful information about two factors that may have substantial interaction but require further investigation. Trial registration: This prospective study has been registered at (NCT03956641), May, 2019.

RevDate: 2020-09-08

Zhao D, Wang H, Chen S, et al (2020)

Phytomelatonin: An Emerging Regulator of Plant Biotic Stress Resistance.

Trends in plant science pii:S1360-1385(20)30256-9 [Epub ahead of print].

Melatonin has diverse functions in plant development and stress tolerance, with recent evidence showing a beneficial role in plant biotic stress tolerance. It has been hypothesized that pathogenic invasion causes the immediate generation of melatonin, reactive oxygen species (ROS), and reactive nitrogen species (RNS), with these being mutually dependent, forming the integrative melatonin-ROS-RNS feedforward loop. Here we discuss how the loop, possibly located in the mitochondria and chloroplasts, maximizes disease resistance in the early pathogen ingress stage, providing on-site protection. We also review how melatonin interacts with phytohormone signaling pathways to mediate defense responses and discuss the evolutionary context from the beginnings of the melatonin receptor-mitogen-activated protein kinase (MAPK) cascade in unicellular green algae, followed by the occurrence of phytohormone pathways in land plants.

RevDate: 2020-11-10

Royes J, Biou V, Dautin N, et al (2020)

Inducible intracellular membranes: molecular aspects and emerging applications.

Microbial cell factories, 19(1):176.

Membrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: (1) they promote the formation of highly curved membrane domains and (2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).

RevDate: 2020-10-20

Karakaidos P, T Rampias (2020)

Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity.

Life (Basel, Switzerland), 10(9):.

In eukaryotic cells, mitochondria originated in an α-proteobacterial endosymbiont. Although these organelles harbor their own genome, the large majority of genes, originally encoded in the endosymbiont, were either lost or transferred to the nucleus. As a consequence, mitochondria have become semi-autonomous and most of their processes require the import of nuclear-encoded components to be functional. Therefore, the mitochondrial-specific translation has evolved to be coordinated by mitonuclear interactions to respond to the energetic demands of the cell, acquiring unique and mosaic features. However, mitochondrial-DNA-encoded genes are essential for the assembly of the respiratory chain complexes. Impaired mitochondrial function due to oxidative damage and mutations has been associated with numerous human pathologies, the aging process, and cancer. In this review, we highlight the unique features of mitochondrial protein synthesis and provide a comprehensive insight into the mitonuclear crosstalk and its co-evolution, as well as the vulnerabilities of the animal mitochondrial genome.

RevDate: 2020-10-12
CmpDate: 2020-09-30

Yazaki E, Kume K, Shiratori T, et al (2020)

Barthelonids represent a deep-branching metamonad clade with mitochondrion-related organelles predicted to generate no ATP.

Proceedings. Biological sciences, 287(1934):20201538.

We here report the phylogenetic position of barthelonids, small anaerobic flagellates previously examined using light microscopy alone. Barthelona spp. were isolated from geographically distinct regions and we established five laboratory strains. Transcriptomic data generated from one Barthelona strain (PAP020) were used for large-scale, multi-gene phylogenetic (phylogenomic) analyses. Our analyses robustly placed strain PAP020 at the base of the Fornicata clade, indicating that barthelonids represent a deep-branching metamonad clade. Considering the anaerobic/microaerophilic nature of barthelonids and preliminary electron microscopy observations on strain PAP020, we suspected that barthelonids possess functionally and structurally reduced mitochondria (i.e. mitochondrion-related organelles or MROs). The metabolic pathways localized in the MRO of strain PAP020 were predicted based on its transcriptomic data and compared with those in the MROs of fornicates. We here propose that strain PAP020 is incapable of generating ATP in the MRO, as no mitochondrial/MRO enzymes involved in substrate-level phosphorylation were detected. Instead, we detected a putative cytosolic ATP-generating enzyme (acetyl-CoA synthetase), suggesting that strain PAP020 depends on ATP generated in the cytosol. We propose two separate losses of substrate-level phosphorylation from the MRO in the clade containing barthelonids and (other) fornicates.

RevDate: 2020-11-12

Seeliger B, Alesina PF, Walz MK, et al (2020)

Intraoperative imaging for remnant viability assessment in bilateral posterior retroperitoneoscopic partial adrenalectomy in an experimental model.

The British journal of surgery, 107(13):1780-1790.

BACKGROUND: A surgical approach preserving functional adrenal tissue allows biochemical cure while avoiding the need for lifelong steroid replacement. The aim of this experimental study was to evaluate the impact of intraoperative imaging during bilateral partial adrenalectomy on remnant perfusion and function.

METHODS: Five pigs underwent bilateral posterior retroperitoneoscopic central adrenal gland division (9 divided glands, 1 undivided). Intraoperative perfusion assessment included computer-assisted quantitative fluorescence imaging, contrast-enhanced CT, confocal laser endomicroscopy (CLE) and local lactate sampling. Specimen analysis after completion adrenalectomy (10 adrenal glands) comprised mitochondrial activity and electron microscopy.

RESULTS: Fluorescence signal intensity evolution over time was significantly lower in the cranial segment of each adrenal gland (mean(s.d.) 0·052(0·057) versus 0·133(0·057) change in intensity per s for cranial versus caudal parts respectively; P = 0·020). Concordantly, intraoperative CT in the portal phase demonstrated significantly lower contrast uptake in cranial segments (P = 0·031). In CLE, fluorescein contrast was observed in all caudal segments, but in only four of nine cranial segments (P = 0·035). Imaging findings favouring caudal perfusion were congruent, with significantly lower local capillary lactate levels caudally (mean(s.d.) 5·66(5·79) versus 11·58(6·53) mmol/l for caudal versus cranial parts respectively; P = 0·008). Electron microscopy showed more necrotic cells cranially (P = 0·031). There was no disparity in mitochondrial activity (respiratory rates, reactive oxygen species and hydrogen peroxide production) between the different segments.

CONCLUSION: In a model of bilateral partial adrenalectomy, three intraoperative imaging modalities consistently discriminated between regular and reduced adrenal remnant perfusion. By avoiding circumferential dissection, mitochondrial function was preserved in each segment of the adrenal glands. Surgical relevance Preservation of adrenal tissue to maintain postoperative function is essential in bilateral and hereditary adrenal pathologies. There is interindividual variation in residual adrenocortical stress capacity, and the minimal functional remnant size is unknown. New intraoperative imaging technologies allow improved remnant size and perfusion assessment. Fluorescence imaging and contrast-enhanced intraoperative CT showed congruent results in evaluation of perfusion. Intraoperative imaging can help to visualize the remnant vascular supply in partial adrenalectomy. Intraoperative assessment of perfusion may foster maximal functional tissue preservation in bilateral adrenal pathologies and procedures.

RevDate: 2020-11-10

Dawson ER, Patananan AN, Sercel AJ, et al (2020)

Stable retention of chloramphenicol-resistant mtDNA to rescue metabolically impaired cells.

Scientific reports, 10(1):14328.

The permanent transfer of specific mtDNA sequences into mammalian cells could generate improved models of mtDNA disease and support future cell-based therapies. Previous studies documented multiple biochemical changes in recipient cells shortly after mtDNA transfer, but the long-term retention and function of transferred mtDNA remains unknown. Here, we evaluate mtDNA retention in new host cells using 'MitoPunch', a device that transfers isolated mitochondria into mouse and human cells. We show that newly introduced mtDNA is stably retained in mtDNA-deficient (ρ0) recipient cells following uridine-free selection, although exogenous mtDNA is lost from metabolically impaired, mtDNA-intact (ρ+) cells. We then introduced a second selective pressure by transferring chloramphenicol-resistant mitochondria into chloramphenicol-sensitive, metabolically impaired ρ+ mouse cybrid cells. Following double selection, recipient cells with mismatched nuclear (nDNA) and mitochondrial (mtDNA) genomes retained transferred mtDNA, which replaced the endogenous mutant mtDNA and improved cell respiration. However, recipient cells with matched mtDNA-nDNA failed to retain transferred mtDNA and sustained impaired respiration. Our results suggest that exogenous mtDNA retention in metabolically impaired ρ+ recipients depends on the degree of recipient mtDNA-nDNA co-evolution. Uncovering factors that stabilize exogenous mtDNA integration will improve our understanding of in vivo mitochondrial transfer and the interplay between mitochondrial and nuclear genomes.

RevDate: 2020-11-24

Medini H, Cohen T, D Mishmar (2020)

Mitochondria Are Fundamental for the Emergence of Metazoans: On Metabolism, Genomic Regulation, and the Birth of Complex Organisms.

Annual review of genetics, 54:151-166.

Out of many intracellular bacteria, only the mitochondria and chloroplasts abandoned their independence billions of years ago and became endosymbionts within the host eukaryotic cell. Consequently, one cannot grow eukaryotic cells without their mitochondria, and the mitochondria cannot divide outside of the cell, thus reflecting interdependence. Here, we argue that such interdependence underlies the fundamental role of mitochondrial activities in the emergence of metazoans. Several lines of evidence support our hypothesis: (a) Differentiation and embryogenesis rely on mitochondrial function; (b) mitochondrial metabolites are primary precursors for epigenetic modifications (such as methyl and acetyl), which are critical for chromatin remodeling and gene expression, particularly during differentiation and embryogenesis; and (c) mitonuclear coregulation adapted to accommodate both housekeeping and tissue-dependent metabolic needs. We discuss the evolution of the unique mitochondrial genetic system, mitochondrial metabolites, mitonuclear coregulation, and their critical roles in the emergence of metazoans and in human disorders.

RevDate: 2020-11-10
CmpDate: 2020-11-10

Li SJ, Zhang X, Lukeš J, et al (2020)

Novel organization of mitochondrial minicircles and guide RNAs in the zoonotic pathogen Trypanosoma lewisi.

Nucleic acids research, 48(17):9747-9761.

Kinetoplastid flagellates are known for several unusual features, one of which is their complex mitochondrial genome, known as kinetoplast (k) DNA, composed of mutually catenated maxi- and minicircles. Trypanosoma lewisi is a member of the Stercorarian group of trypanosomes which is, based on human infections and experimental data, now considered a zoonotic pathogen. By assembling a total of 58 minicircle classes, which fall into two distinct categories, we describe a novel type of kDNA organization in T. lewisi. RNA-seq approaches allowed us to map the details of uridine insertion and deletion editing events upon the kDNA transcriptome. Moreover, sequencing of small RNA molecules enabled the identification of 169 unique guide (g) RNA genes, with two differently organized minicircle categories both encoding essential gRNAs. The unprecedented organization of minicircles and gRNAs in T. lewisi broadens our knowledge of the structure and expression of the mitochondrial genomes of these human and animal pathogens. Finally, a scenario describing the evolution of minicircles is presented.

RevDate: 2020-08-27

Arakawa T, Kagami H, Katsuyama T, et al (2020)

A lineage-specific paralogue of Oma1 evolved into a gene family from which a suppressor of male sterility-inducing mitochondria emerged in plants.

Genome biology and evolution pii:5898194 [Epub ahead of print].

Cytoplasmic male sterility in plants is caused by male sterility-inducing mitochondria, which have emerged frequently during plant evolution. Nuclear Restorer-of-fertility (Rf) genes can suppress their cognate male sterility-inducing mitochondria. Whereas many Rfs encode a class of RNA binding protein, the sugar beet (Caryophyllales) Rf encodes a protein resembling Oma1, which is involved in the quality control of mitochondria. In this study we investigated the molecular evolution of Oma1 homologues in plants. We analyzed 37 plant genomes and concluded that a single copy is the ancestral state in Caryophyllales. Among the sugar beet Oma1 homologues, the orthologous copy is located in a syntenic region that is preserved in Arabidopsis thaliana. The sugar beet Rf is a complex locus consisting of a small Oma1 homologue family (RF-Oma1 family) unique to sugar beet. The gene arrangement in the vicinity of the locus is seen in some but not all Caryophyllalean plants and is absent from A. thaliana. This suggests a segmental duplication rather than a whole genome duplication as the mechanism of RF-Oma1 evolution. Among the positively selected codons in RF-Oma1, many are located in predicted transmembrane helices. Phylogenetic network analysis indicated that homologous recombination among the RF-Oma1 members played an important role to generate protein activity related to suppression. Together, our data illustrate how an evolutionarily young Rf has emerged from a lineage-specific paralogue. Interestingly, several evolutionary features are shared with the RNA binding protein type Rfs. Hence, the evolution of the sugar beet Rf is representative of Rf evolution in general.

RevDate: 2020-08-28

Pérez-Hernández CA, Kern CC, Butkeviciute E, et al (2020)

Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.

Frontiers in immunology, 11:1715.

Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, than untrained monocytes. Candida albicans, β-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca2+ uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.

RevDate: 2020-09-28

Aguirre-López B, Escalera-Fanjul X, Hersch-González J, et al (2020)

In Kluyveromyces lactis a Pair of Paralogous Isozymes Catalyze the First Committed Step of Leucine Biosynthesis in Either the Mitochondria or the Cytosol.

Frontiers in microbiology, 11:1843.

Divergence of paralogous pairs, resulting from gene duplication, plays an important role in the evolution of specialized or novel gene functions. Analysis of selected duplicated pairs has elucidated some of the mechanisms underlying the functional diversification of Saccharomyces cerevisiae (S. cerevisiae) paralogous genes. Similar studies of the orthologous pairs extant in pre-whole genome duplication yeast species, such as Kluyveromyces lactis (K. lactis) remain to be addressed. The genome of K. lactis, an aerobic yeast, includes gene pairs generated by sporadic duplications. The genome of this organism comprises the KlLEU4 and KlLEU4BIS paralogous pair, annotated as putative α-isopropylmalate synthases (α-IPMSs), considered to be the orthologs of the S. cerevisiae ScLEU4/ScLEU9 paralogous genes. The enzymes encoded by the latter two genes are mitochondrially located, differing in their sensitivity to leucine allosteric inhibition resulting in ScLeu4-ScLeu4 and ScLeu4-ScLeu9 sensitive dimers and ScLeu9-ScLeu9 relatively resistant homodimers. Previous work has shown that, in a Scleu4Δ mutant, ScLEU9 expression is increased and assembly of ScLeu9-ScLeu9 leucine resistant homodimers results in loss of feedback regulation of leucine biosynthesis, leading to leucine accumulation and decreased growth rate. Here we report that: (i) K. lactis harbors a sporadic gene duplication, comprising the KlLEU4, syntenic with S. cerevisiae ScLEU4 and ScLEU9, and the non-syntenic KlLEU4BIS, arising from a pre-WGD event. (ii) That both, KlLEU4 and KlLEU4BIS encode leucine sensitive α-IPMSs isozymes, located in the mitochondria (KlLeu4) and the cytosol (KlLeu4BIS), respectively. (iii) That both, KlLEU4 or KlLEU4BIS complement the Scleu4Δ Scleu9Δ leucine auxotrophic phenotype and revert the enhanced ScLEU9 transcription observed in a Scleu4Δ ScLEU9 mutant. The Scleu4Δ ScLEU9 growth mutant phenotype is only fully complemented when transformed with the syntenic KlLEU4 mitochondrial isoform. KlLEU4 and KlLEU4BIS underwent a different diversification pathways than that leading to ScLEU4/ScLEU9. KlLEU4 could be considered as the functional ortholog of ScLEU4, since its encoded isozyme can complement both the Scleu4Δ Scleu9Δ leucine auxotrophy and the Scleu4Δ ScLEU9 complex phenotype.

RevDate: 2020-09-28

Chen M, Chen N, Wu T, et al (2020)

Characterization of Two Mitochondrial Genomes and Gene Expression Analysis Reveal Clues for Variations, Evolution, and Large-Sclerotium Formation in Medical Fungus Wolfiporia cocos.

Frontiers in microbiology, 11:1804.

Wolfiporia cocos, a precious mushroom with a long history as an edible food and Asian traditional medicine, remains unclear in the genetic mechanism underlying the formation of large sclerotia. Here, two complete circular mitogenomes (BL16, 135,686 bp and MD-104 SS10, 124,842 bp, respectively) were presented in detail first. The salient features in the mitogenomes of W. cocos include an intron in the tRNA (trnQ-UUG2), and an obvious gene rearrangement identified between the two mitogenomes from the widely geographically separated W. cocos strains. Genome comparison and phylogenetic analyses reveal some variations and evolutional characteristics in W. cocos. Whether the mitochondrion is functional in W. cocos sclerotium development was investigated by analyzing the mitogenome synteny of 10 sclerotium-forming fungi and mitochondrial gene expression patterns in different W. cocos sclerotium-developmental stages. Three common homologous genes identified across ten sclerotium-forming fungi were also found to exhibit significant differential expression levels during W. cocos sclerotium development. Most of the mitogenomic genes are not expressed in the mycelial stage but highly expressed in the sclerotium initial or developmental stage. These results indicate that some of mitochondrial genes may play a role in the development of sclerotium in W. cocos, which needs to be further elucidated in future studies. This study will stimulate new ideas on cytoplasmic inheritance of W. cocos and facilitate the research on the role of mitochondria in large sclerotium formation.

RevDate: 2020-10-27

Nunes-Nesi A, Cavalcanti JHF, AR Fernie (2020)

Characterization of In Vivo Function(s) of Members of the Plant Mitochondrial Carrier Family.

Biomolecules, 10(9):.

Although structurally related, mitochondrial carrier family (MCF) proteins catalyze the specific transport of a range of diverse substrates including nucleotides, amino acids, dicarboxylates, tricarboxylates, cofactors, vitamins, phosphate and H+. Despite their name, they do not, however, always localize to the mitochondria, with plasma membrane, peroxisomal, chloroplast and thylakoid and endoplasmic reticulum localizations also being reported. The existence of plastid-specific MCF proteins is suggestive that the evolution of these proteins occurred after the separation of the green lineage. That said, plant-specific MCF proteins are not all plastid-localized, with members also situated at the endoplasmic reticulum and plasma membrane. While by no means yet comprehensive, the in vivo function of a wide range of these transporters is carried out here, and we discuss the employment of genetic variants of the MCF as a means to provide insight into their in vivo function complementary to that obtained from studies following their reconstitution into liposomes.

RevDate: 2020-11-02

Esch T, Kream RM, GB Stefano (2020)

Emerging regulatory roles of opioid peptides, endogenous morphine, and opioid receptor subtypes in immunomodulatory processes: Metabolic, behavioral, and evolutionary perspectives.

Immunology letters, 227:28-33.

Integrated behavioral paradigms such as nociceptive processing coupled to anti-nociceptive responsiveness include systemically-mediated states of alertness, vigilance, motivation, and avoidance. Within a historical and cultural context, opium and its biologically active compounds, codeine and morphine, have been widely used as frontline anti-nociceptive agents. In eukaryotic cells, opiate alkaloids and opioid peptides were evolutionarily fashioned as regulatory factors in neuroimmune, vascular immune, and systemic immune communication and auto-immunoregulation. The significance of opioidergic regulation of immune function was validated by the identification of novel μ and δ opioid receptors on circulating leukocytes. The novel μ3 opioid receptor subtype has been characterized as an opioid peptide-insensitive and opiate alkaloid-selective G protein-coupled receptor (GPCR) that is functionally linked to the activation of constitutive nitric oxide synthase (cNOS). Opioid peptides stimulate granulocyte and immunocyte activation and chemotaxis via activation of a novel leukocyte δ2 receptor subtype. However, opiate alkaloid μ3 receptor agonists inhibit these same cellular activities. Opiate coupling to cNOS and subsequent production and release of mitochondrial nitric oxide (NO) suggests an evolutionary linkage to similar physiological events in prokaryotic cells. A subpopulation of immunocytes from Mytilus edulis and Leucophaea maderae and human granulocytes respond to low opioid concentrations, mediated by the adherence-promoting role of (D-Ala2-D-Met5)-enkephalinamide (DAMA), which is blocked by naloxone in a dose-dependent manner. Neutral endopeptidase 24.11 (NEP), or enkephalinase (CD10), is present on both human and invertebrate immunocytes. Alkaloids, including morphine, are found in both prokaryotic and eukaryotic cells and may have evolved much later in evolution through horizontal gene transfer. It is possible that opioid-mediated regulatory activities were conserved and elaborated during evolution as the central nervous system (CNS) became immunologically isolated by the blood-brain barrier. Thus, opioid receptor coupling became significant for cognitive and behavioural processes. Although opioid peptides and alkaloids work synergistically to suppress nociception, they mediate different actions in immune surveillance. Increased understanding of the evolutionary development of opioid receptors, nociceptive and anti-nociceptive pathways, and immunomodulation may help in the understanding of the development of tolerance to the clinical use of opiates for pain management. The significance of endogenous morphine's importance to evolution can be ascertained by the number of physiological tissues and systems that can be affected by this chemical messenger mechanism, which transcends pain. An integrated review is presented of opioid and opiate receptors, immunomodulation, and pain associated with inflammation, from an evolutionary perspective.

RevDate: 2020-09-24

Shen H, Zheng X, Zhou Z, et al (2020)

Oriented immobilization of enzyme-DNA conjugates on magnetic Janus particles for constructing a multicompartment multienzyme system with high activity and stability.

Journal of materials chemistry. B, 8(36):8467-8475.

Various organelles (e.g., mitochondria and chloroplasts) have a multicompartment structure, providing superior function of material transformation, selective segregation and energy conversion. Enlightened by the elegant evolution of nature, intended isolation of the biochemical process by cooperative multicompartments in cells has become an appealing blueprint to construct bioreactors. In this study, we develop a "soft separation" way to establish a delicate multicompartment multienzyme system (MMS) with polyphenol-encapsulated enzyme-DNA conjugates, which are anchored on magnetic Janus particles, providing a biomimetic catalysis network with the model cascade reactions in confinement. The well-designed MMS exhibits preferable bioactivity benefitting from the dependable DNA bridges and the oriented immobilization of enzymes, while the polyphenol shell further protects the anchored enzymes from exterior attacks, such as heat and enzymatic degradation. Moreover, by applying the MMS as nanomotors, the asymmetrical distribution of enzymes on Janus particles is found to improve mutual elevation between the self-driven locomotion and enzyme-mediated reactions, delivering enhanced dispersal ability and bioactivity. Owing to the excellent enzymatic activity, promoted stability and satisfying biocompatibility, the assembled MMS is proved to be promising for the in vitro and intracellular sensing of glucose, showing significant potential for biochemical analysis applications.

RevDate: 2020-09-28

Santos HJ, Chiba Y, Makiuchi T, et al (2020)

Import of Entamoeba histolytica Mitosomal ATP Sulfurylase Relies on Internal Targeting Sequences.

Microorganisms, 8(8):.

Mitochondrial matrix proteins synthesized in the cytosol often contain amino (N)-terminal targeting sequences (NTSs), or alternately internal targeting sequences (ITSs), which enable them to be properly translocated to the organelle. Such sequences are also required for proteins targeted to mitochondrion-related organelles (MROs) that are present in a few species of anaerobic eukaryotes. Similar to other MROs, the mitosomes of the human intestinal parasite Entamoeba histolytica are highly degenerate, because a majority of the components involved in various processes occurring in the canonical mitochondria are either missing or modified. As of yet, sulfate activation continues to be the only identified role of the relic mitochondria of Entamoeba. Mitosomes influence the parasitic nature of E. histolytica, as the downstream cytosolic products of sulfate activation have been reported to be essential in proliferation and encystation. Here, we investigated the position of the targeting sequence of one of the mitosomal matrix enzymes involved in the sulfate activation pathway, ATP sulfurylase (AS). We confirmed by immunofluorescence assay and subcellular fractionation that hemagluttinin (HA)-tagged EhAS was targeted to mitosomes. However, its ortholog in the δ-proteobacterium Desulfovibrio vulgaris, expressed as DvAS-HA in amoebic trophozoites, indicated cytosolic localization, suggesting a lack of recognizable mitosome targeting sequence in this protein. By expressing chimeric proteins containing swapped sequences between EhAS and DvAS in amoebic cells, we identified the ITSs responsible for mitosome targeting of EhAS. This observation is similar to other parasitic protozoans that harbor MROs, suggesting a convergent feature among various MROs in favoring ITS for the recognition and translocation of targeted proteins.

RevDate: 2020-09-28

N Miyata M, Nomura M, D Kageyama (2020)

Wolbachia have made it twice: Hybrid introgression between two sister species of Eurema butterflies.

Ecology and evolution, 10(15):8323-8330.

Wolbachia, cytoplasmically inherited endosymbionts of arthropods, are known to hijack their host reproduction in various ways to increase their own vertical transmission. This may lead to the selective sweep of associated mitochondria, which can have a large impact on the evolution of mitochondrial lineages. In Japan, two different Wolbacahia strains (wCI and wFem) are found in two sister species of pierid butterflies, Eurema mandarina and Eurema hecabe. In both species, females infected with wCI (C females) produce offspring with a nearly 1:1 sex ratio, while females infected with both wCI and wFem (CF females) produce all-female offspring. Previous studies have suggested the historical occurrence of hybrid introgression in C individuals between the two species. Furthermore, hybrid introgression in CF individuals is suggested by the distinct mitochondrial lineages between C females and CF females of E. mandarina. In this study, we performed phylogenetic analyses based on nuclear DNA and mitochondrial DNA markers of E. hecabe with previously published data on E. mandarina. We found that the nuclear DNA of this species significantly diverged from that of E. mandarina. By contrast, mitochondrial DNA haplotypes comprised two clades, mostly reflecting Wolbachia infection status rather than the individual species. Collectively, our results support the previously suggested occurrence of two independent historical events wherein the cytoplasms of CF females and C females moved between E. hecabe and E. mandarina through hybrid introgression.

RevDate: 2020-09-09
CmpDate: 2020-09-09

Pittis AA, Goh V, Cebrian-Serrano A, et al (2020)

Discovery of EMRE in fungi resolves the true evolutionary history of the mitochondrial calcium uniporter.

Nature communications, 11(1):4031.

Calcium (Ca2+) influx into mitochondria occurs through a Ca2+-selective uniporter channel, which regulates essential cellular processes in eukaryotic organisms. Previous evolutionary analyses of its pore-forming subunits MCU and EMRE, and gatekeeper MICU1, pinpointed an evolutionary paradox: the presence of MCU homologs in fungal species devoid of any other uniporter components and of mt-Ca2+ uptake. Here, we trace the mt-Ca2+ uniporter evolution across 1,156 fully-sequenced eukaryotes and show that animal and fungal MCUs represent two distinct paralogous subfamilies originating from an ancestral duplication. Accordingly, we find EMRE orthologs outside Holoza and uncover the existence of an animal-like uniporter within chytrid fungi, which enables mt-Ca2+ uptake when reconstituted in vivo in the yeast Saccharomyces cerevisiae. Our study represents the most comprehensive phylogenomic analysis of the mt-Ca2+ uptake system and demonstrates that MCU, EMRE, and MICU formed the core of the ancestral opisthokont uniporter, with major implications for comparative structural and functional studies.

RevDate: 2020-09-07

Bennewitz B, Sharma M, Tannert F, et al (2020)

Dual targeting of TatA points to a chloroplast-like Tat pathway in plant mitochondria.

Biochimica et biophysica acta. Molecular cell research, 1867(11):118816.

The biogenesis of membrane-bound electron transport chains requires membrane translocation pathways for folded proteins carrying complex cofactors, like the Rieske Fe/S proteins. Two independent systems were developed during evolution, namely the Twin-arginine translocation (Tat) pathway, which is present in bacteria and chloroplasts, and the Bcs1 pathway found in mitochondria of yeast and mammals. Mitochondria of plants carry a Tat-like pathway which was hypothesized to operate with only two subunits, a TatB-like protein and a TatC homolog (OrfX), but lacking TatA. Here we show that the nuclearly encoded TatA from pea has dual targeting properties, i.e., it can be imported into both, chloroplasts and mitochondria. Dual targeting of TatA was observed with in organello experiments employing chloroplasts and mitochondria isolated from pea as well as after transient expression of suitable reporter constructs in leaf tissue from pea and Nicotiana benthamiana. The extent of transport of these constructs into mitochondria of transiently transformed leaf cells was relatively low, causing a demand for highly sensitive methods to be detected, like the sasplitGFP approach. Yet, the dual import of TatA into mitochondria and chloroplasts observed here points to a common mechanism of Tat transport for folded proteins within both endosymbiotic organelles in plants.

RevDate: 2020-09-07

Nechushtai R, Karmi O, Zuo K, et al (2020)

The balancing act of NEET proteins: Iron, ROS, calcium and metabolism.

Biochimica et biophysica acta. Molecular cell research, 1867(11):118805.

NEET proteins belong to a highly conserved group of [2Fe-2S] proteins found across all kingdoms of life. Due to their unique [2Fe2S] cluster structure, they play a key role in the regulation of many different redox and oxidation processes. In eukaryotes, NEET proteins are localized to the mitochondria, endoplasmic reticulum (ER) and the mitochondrial-associated membranes connecting these organelles (MAM), and are involved in the control of multiple processes, ranging from autophagy and apoptosis to ferroptosis, oxidative stress, cell proliferation, redox control and iron and iron‑sulfur homeostasis. Through their different functions and interactions with key proteins such as VDAC and Bcl-2, NEET proteins coordinate different mitochondrial, MAM, ER and cytosolic processes and functions and regulate major signaling molecules such as calcium and reactive oxygen species. Owing to their central role in cells, NEET proteins are associated with numerous human maladies including cancer, metabolic diseases, diabetes, obesity, and neurodegenerative diseases. In recent years, a new and exciting role for NEET proteins was uncovered, i.e., the regulation of mitochondrial dynamics and morphology. This new role places NEET proteins at the forefront of studies into cancer and different metabolic diseases, both associated with the regulation of mitochondrial dynamics. Here we review recent studies focused on the evolution, biological role, and structure of NEET proteins, as well as discuss different studies conducted on NEET proteins function using transgenic organisms. We further discuss the different strategies used in the development of drugs that target NEET proteins, and link these with the different roles of NEET proteins in cells.

RevDate: 2020-08-02

Smith SK, ES Musiek (2020)

Impact of circadian and diurnal rhythms on cellular metabolic function and neurodegenerative diseases.

International review of neurobiology, 154:393-412.

The 24-h rotational period of the earth has driven evolution of biological systems that serve to synchronize organismal physiology and behavior to this predictable environmental event. In mammals, the circadian (circa, "about" and dia, "a day") clock keeps 24-h time at the organismal and cellular level, optimizing biological function for a given time of day. The most obvious circadian output is the sleep-wake cycle, though countless bodily functions, ranging from hormone levels to cognitive function, are influenced by the circadian clock. Here we discuss the regulation of metabolic pathways by the circadian clock, discuss the evidence implicating circadian and sleep disruption in neurodegenerative diseases, and suggest some possible connections between the clock, metabolism, and neurodegenerative disease.

RevDate: 2020-10-02

Williams R, Laskovs M, Williams RI, et al (2020)

A Mitochondrial Stress-Specific Form of HSF1 Protects against Age-Related Proteostasis Collapse.

Developmental cell, 54(6):758-772.e5.

The loss of protein homeostasis (proteostasis) is a primary driver of age-related tissue dysfunction. Recent studies have revealed that the failure of proteostasis with age is triggered by developmental and reproductive cues that repress the activity of proteostasis-related pathways in early adulthood. In Caenorhabditis elegans, reduced mitochondrial electron transport chain (ETC) function during development can override signals that promote proteostasis collapse in aged tissues. However, it is unclear precisely how these beneficial effects are mediated. Here, we reveal that in response to ETC impairment, the PP2A complex generates a dephosphorylated, mitochondrial stress-specific variant of the transcription factor HSF-1. This results in the selective induction of small heat shock proteins in adulthood, thereby protecting against age-related proteostasis collapse. We propose that mitochondrial signals early in life can protect the aging cytosolic proteome by tailoring HSF-1 activity to preferentially drive the expression of non-ATP-dependent chaperones.

RevDate: 2020-09-29
CmpDate: 2020-09-29

Pelster B, Wood CM, Campos DF, et al (2020)

Cellular oxygen consumption, ROS production and ROS defense in two different size-classes of an Amazonian obligate air-breathing fish (Arapaima gigas).

PloS one, 15(7):e0236507.

In air-breathing fish a reduction of gill surface area reduces the danger of losing oxygen taken up in the air-breathing organ (ABO) to hypoxic water, but it also reduces the surface area available for ion exchange, so that ion regulation may at least in part be transferred to other organs, like the kidney or the gut. In the air-breathing Arapaima gigas, gill lamellae regress as development proceeds, and starting as a water-breathing embryo Arapaima turns into an obligate air-breathing fish with proceeding development, suggesting that ion regulation is shifted away from the gills as the fish grows. In Arapaima the kidney projects medially into the ABO and thus, probably a unique situation among fishes, is in close contact to the gas of the ABO. We therefore hypothesized that the kidney would be predestined to adopt an increased importance for ion homeostasis, because the elevated ATP turnover connected to ion transport can easily be met by aerobic metabolism based on the excellent oxygen supply directly from the ABO. We also hypothesized that in gill tissue the reduced ion regulatory activity should result in a reduced metabolic activity. High metabolic activity and exposure to high oxygen tensions are connected to the production of reactive oxygen species (ROS), therefore the tissues exposed to these conditions should have a high ROS defense capacity. Using in vitro studies, we assessed metabolic activity and ROS production of gill, kidney and ABO tissue, and determined the activity of ROS degrading enzymes in small (~ 5g, 2-3 weeks old) and larger (~ 670 g, 3-4 months old) A. gigas. Comparing the three tissues revealed that kidney tissue oxygen uptake by far exceeded the uptake measured in gill tissue or ABO. ROS production was particularly high in gill tissue, and all three tissues had a high capacity to degrade ROS. Gill tissue was characterized by high activities of enzymes involved in the glutathione pathway to degrade ROS. By contrast, the tissues of the ABO and in particular the kidney were characterized by high catalase activities, revealing different, tissue-specific strategies in ROS defense in this species. Overall the differences in the activity of cells taken from small and larger fish were not as pronounced as expected, while at the tissue level the metabolic activity of kidney cells by far exceeded the activity of ABO and gill cells.

RevDate: 2020-08-05

Wang X, Wang J, Liu J, et al (2020)

Insights into the phylogenetic relationships and drug targets of Babesia isolates infective to small ruminants from the mitochondrial genomes.

Parasites & vectors, 13(1):378.

BACKGROUND: Babesiosis, a tick-borne disease caused by protozoans of the genus Babesia, is widespread in subtropical and tropical countries. Mitochondria are essential organelles that are responsible for energy transduction and metabolism, calcium homeostasis and cell signaling. Mitochondrial genomes could provide new insights to help elucidate and investigate the biological features, genetic evolution and classification of the protozoans. Nevertheless, there are limited data on the mitochondrial genomes of ovine Babesia spp. in China.

METHODS: Herein, we sequenced, assembled and annotated the mitochondrial genomes of six ovine Babesia isolates; analyzed the genome size, gene content, genome structure and cytochrome b (cytb) amino acid sequences and performed comparative mitochondrial genomics and phylogenomic analyses among apicomplexan parasites.

RESULTS: The mitochondrial genomes range from 5767 to 5946 bp in length with a linear form and contain three protein-encoding genes, cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 3 (cox3) and cytb, six large subunit rRNA genes (LSU) and two terminal inverted repeats (TIR) on both ends. The cytb gene sequence analysis indicated the binding site of anti-Babesia drugs that targeted the cytochrome bc1 complex. Babesia microti and Babesia rodhaini have a dual flip-flop inversion of 184-1082 bp, whereas other Babesia spp. and Theileria spp. have one pair of TIRs, 25-1563 bp. Phylogenetic analysis indicated that the six ovine Babesia isolates were divided into two clades, Babesia sp. and Babesia motasi. Babesia motasi isolates were further separated into two small clades (B. motasi Hebei/Ningxian and B. motasi Tianzhu/Lintan).

CONCLUSIONS: The data provided new insights into the taxonomic relationships and drug targets of apicomplexan parasites.

RevDate: 2020-09-09
CmpDate: 2020-09-09

Fernando HSD, Hapugoda M, Perera R, et al (2020)

Mitochondrial metabolic genes provide phylogeographic relationships of global collections of Aedes aegypti (Diptera: Culicidae).

PloS one, 15(7):e0235430.

Phylogeographic relationships among global collections of the mosquito Aedes aegypti were evaluated using the mitochondrial Cytochrome C Oxidase 1 (CO1) and NADH dehydrogenase subunit 4 (ND4) genes including new sequences from Sri Lanka. Phylogeographic analysis estimated that Ae. aegypti arose as a species ~614 thousand years ago (kya) in the late Pleistocene. At 545 kya an "early" East African clade arose that continued to differentiate in East Africa, and eventually gave rise to three lineages one of which is distributed throughout all tropical and subtropical regions, a second that contains Southeast Asian/Sri Lankan mosquitoes and a third that contains mostly New World mosquitoes. West African collections were not represented in this early clade. The late clade continued to differentiate throughout Africa and gave rise to a lineage that spread globally. The most recent branches of the late clade are represented by South-East Asia and India/Pakistan collections. Analysis of migration rates suggests abundant gene flow between India/Pakistan and the rest of the world with the exception of Africa.

RevDate: 2020-10-23

Flament-Simon SC, de Toro M, Chuprikova L, et al (2020)

High diversity and variability of pipolins among a wide range of pathogenic Escherichia coli strains.

Scientific reports, 10(1):12452.

Self-synthesizing transposons are integrative mobile genetic elements (MGEs) that encode their own B-family DNA polymerase (PolB). Discovered a few years ago, they are proposed as key players in the evolution of several groups of DNA viruses and virus-host interaction machinery. Pipolins are the most recent addition to the group, are integrated in the genomes of bacteria from diverse phyla and also present as circular plasmids in mitochondria. Remarkably, pipolins-encoded PolBs are proficient DNA polymerases endowed with DNA priming capacity, hence the name, primer-independent PolB (piPolB). We have now surveyed the presence of pipolins in a collection of 2,238 human and animal pathogenic Escherichia coli strains and found that, although detected in only 25 positive isolates (1.1%), they are present in E. coli strains from a wide variety of pathotypes, serotypes, phylogenetic groups and sequence types. Overall, the pangenome of strains carrying pipolins is highly diverse, despite the fact that a considerable number of strains belong to only three clonal complexes (CC10, CC23 and CC32). Comparative analysis with a set of 67 additional pipolin-harboring genomes from GenBank database spanning strains from diverse origin, further confirmed these results. The genetic structure of pipolins shows great flexibility and variability, with the piPolB gene and the attachment sites being the only common features. Most pipolins contain one or more recombinases that would be involved in excision/integration of the element in the same conserved tRNA gene. This mobilization mechanism might explain the apparent incompatibility of pipolins with other integrative MGEs such as integrons. In addition, analysis of cophylogeny between pipolins and pipolin-harboring strains showed a lack of congruence between several pipolins and their host strains, in agreement with horizontal transfer between hosts. Overall, these results indicate that pipolins can serve as a vehicle for genetic transfer among circulating E. coli and possibly also among other pathogenic bacteria.

RevDate: 2020-11-23

Bertgen L, Mühlhaus T, JM Herrmann (2020)

Clingy genes: Why were genes for ribosomal proteins retained in many mitochondrial genomes?.

Biochimica et biophysica acta. Bioenergetics, 1861(11):148275.

Why mitochondria still retain their own genome is a puzzle given the enormous effort to maintain a mitochondrial translation machinery. Most mitochondrially encoded proteins are membrane-embedded subunits of the respiratory chain. Their hydrophobicity presumably impedes their import into mitochondria. However, many mitochondrial genomes also encode protein subunits of the mitochondrial ribosome. These proteins lack transmembrane domains and hydrophobicity cannot explain why their genes remained in mitochondria. In this review, we provide an overview about mitochondrially encoded subunits of mitochondrial ribosomes of fungi, plants and protists. Moreover, we discuss and evaluate different hypotheses which were put forward to explain why (ribosomal) proteins remained mitochondrially encoded. It seems likely that the synthesis of ribosomal proteins in the mitochondrial matrix is used to regulate the assembly of the mitochondrial ribosome within mitochondria and to avoid problems that mitochondrial proteins might pose for cytosolic proteostasis and for the assembly of cytosolic ribosomes.

RevDate: 2020-11-02
CmpDate: 2020-11-02

Cunnane SC, Trushina E, Morland C, et al (2020)

Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.

Nature reviews. Drug discovery, 19(9):609-633.

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner - a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes.

RevDate: 2020-09-07

Žihala D, Salamonová J, M Eliáš (2020)

Evolution of the genetic code in the mitochondria of Labyrinthulea (Stramenopiles).

Molecular phylogenetics and evolution, 152:106908.

Mitochondrial translation often exhibits departures from the standard genetic code, but the full spectrum of these changes has certainly not yet been described and the molecular mechanisms behind the changes in codon meaning are rarely studied. Here we report a detailed analysis of the mitochondrial genetic code in the stramenopile group Labyrinthulea (Labyrinthulomycetes) and their relatives. In the genus Aplanochytrium, UAG is not a termination codon but encodes tyrosine, in contrast to the unaffected meaning of the UAA codon. This change is evolutionarily independent of the reassignment of both UAG and UAA as tyrosine codons recently reported from two uncultivated labyrinthuleans (S2 and S4), which we show are not thraustochytrids as proposed before, but represent the clade LAB14 previously recognised in environmental 18S rRNA gene surveys. We provide rigorous evidence that the UUA codon in the mitochondria of all labyrinthuleans serves as a termination codon instead of encoding leucine, and propose that a sense-to-stop reassignment has also affected the AGG and AGA codons in the LAB14 clade. The distribution of the different forms of sense-to-stop and stop-to-sense reassignments correlates with specific modifications of the mitochondrial release factor mtRF2a in different subsets of labyrinthuleans, and with the unprecedented loss of mtRF1a in Aplanochytrium and perhaps also in the LAB14 clade, pointing towards a possible mechanistic basis of the code changes observed. Curiously, we show that labyrinthulean mitochondria also exhibit a sense-to-sense codon reassignment, manifested as AUA encoding methionine instead of isoleucine. Furthermore, we show that this change evolved independently in the uncultivated stramenopile lineage MAST8b, together with the reassignment of the AGR codons from arginine to serine. Altogether, our study has uncovered novel variants of the mitochondrial genetic code and previously unknown modifications of the mitochondrial translation machinery, further enriching our understanding of the rules governing the evolution of one of the central molecular process in the cell.

RevDate: 2020-09-15
CmpDate: 2020-09-15

Codo AC, Davanzo GG, Monteiro LB, et al (2020)

Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.

Cell metabolism, 32(3):437-446.e5.

COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.

RevDate: 2020-08-12

Kami D, S Gojo (2020)

From Cell Entry to Engraftment of Exogenous Mitochondria.

International journal of molecular sciences, 21(14):.

Mitochondrial transfer has been recognized to play a role in a variety of processes, ranging from fertilization to cancer and neurodegenerative diseases as well as mammalian horizontal gene transfer. It is achieved through either exogeneous or intercellular mitochondrial transfer. From the viewpoint of evolution, exogeneous mitochondrial transfer is quite akin to the initial process of symbiosis between α-protobacterium and archaea, although the progeny have developed more sophisticated machinery to engulf environmental materials, including nutrients, bacteria, and viruses. A molecular-based knowledge of endocytosis, including macropinocytosis and endosomal escape involving bacteria and viruses, could provide mechanistic insights into exogeneous mitochondrial transfer. We focus on exogeneous mitochondrial transfer in this review to facilitate the clinical development of the use of isolated mitochondria to treat various pathological conditions. Several kinds of novel procedures to enhance exogeneous mitochondrial transfer have been developed and are summarized in this review.

RevDate: 2020-09-28

Praud C, Jimenez J, Pampouille E, et al (2020)

Molecular Phenotyping of White Striping and Wooden Breast Myopathies in Chicken.

Frontiers in physiology, 11:633.

The White Striping (WS) and Wooden Breast (WB) defects are two myopathic syndromes whose occurrence has recently increased in modern fast-growing broilers. The impact of these defects on the quality of breast meat is very important, as they greatly affect its visual aspect, nutritional value, and processing yields. The research conducted to date has improved our knowledge of the biological processes involved in their occurrence, but no solution has been identified so far to significantly reduce their incidence without affecting growing performance of broilers. This study aims to follow the evolution of molecular phenotypes in relation to both fast-growing rate and the occurrence of defects in order to identify potential biomarkers for diagnostic purposes, but also to improve our understanding of physiological dysregulation involved in the occurrence of WS and WB. This has been achieved through enzymatic, histological, and transcriptional approaches by considering breast muscles from a slow- and a fast-growing line, affected or not by WS and WB. Fast-growing muscles produced more reactive oxygen species (ROS) than slow-growing ones, independently of WS and WB occurrence. Within fast-growing muscles, despite higher mitochondria density, muscles affected by WS or WB defects did not show higher cytochrome oxidase activity (COX) activity, suggesting altered mitochondrial function. Among the markers related to muscle remodeling and regeneration, immunohistochemical staining of FN1, NCAM, and MYH15 was higher in fast- compared to slow-growing muscles, and their amount also increased linearly with the presence and severity of WS and WB defects, making them potential biomarkers to assess accurately their presence and severity. Thanks to an innovative histological technique based on fluorescence intensity measurement, they can be rapidly quantified to estimate the injuries induced in case of WS and WB. The muscular expression of several other genes correlates also positively to the presence and severity of the defects like TGFB1 and CTGF, both involved in the development of connective tissue, or Twist1, known as an inhibitor of myogenesis. Finally, our results suggested that a balance between TGFB1 and PPARG would be essential for fibrosis or adiposis induction and therefore for determining WS and WB phenotypes.

RevDate: 2020-08-24
CmpDate: 2020-08-24

Arbeithuber B, Hester J, Cremona MA, et al (2020)

Age-related accumulation of de novo mitochondrial mutations in mammalian oocytes and somatic tissues.

PLoS biology, 18(7):e3000745.

Mutations create genetic variation for other evolutionary forces to operate on and cause numerous genetic diseases. Nevertheless, how de novo mutations arise remains poorly understood. Progress in the area is hindered by the fact that error rates of conventional sequencing technologies (1 in 100 or 1,000 base pairs) are several orders of magnitude higher than de novo mutation rates (1 in 10,000,000 or 100,000,000 base pairs per generation). Moreover, previous analyses of germline de novo mutations examined pedigrees (and not germ cells) and thus were likely affected by selection. Here, we applied highly accurate duplex sequencing to detect low-frequency, de novo mutations in mitochondrial DNA (mtDNA) directly from oocytes and from somatic tissues (brain and muscle) of 36 mice from two independent pedigrees. We found mtDNA mutation frequencies 2- to 3-fold higher in 10-month-old than in 1-month-old mice, demonstrating mutation accumulation during the period of only 9 mo. Mutation frequencies and patterns differed between germline and somatic tissues and among mtDNA regions, suggestive of distinct mutagenesis mechanisms. Additionally, we discovered a more pronounced genetic drift of mitochondrial genetic variants in the germline of older versus younger mice, arguing for mtDNA turnover during oocyte meiotic arrest. Our study deciphered for the first time the intricacies of germline de novo mutagenesis using duplex sequencing directly in oocytes, which provided unprecedented resolution and minimized selection effects present in pedigree studies. Moreover, our work provides important information about the origins and accumulation of mutations with aging/maturation and has implications for delayed reproduction in modern human societies. Furthermore, the duplex sequencing method we optimized for single cells opens avenues for investigating low-frequency mutations in other studies.

RevDate: 2020-08-08

Pedriali G, Morciano G, Patergnani S, et al (2020)

Aortic Valve Stenosis and Mitochondrial Dysfunctions: Clinical and Molecular Perspectives.

International journal of molecular sciences, 21(14):.

Calcific aortic stenosis is a disorder that impacts the physiology of heart valves. Fibrocalcific events progress in conjunction with thickening of the valve leaflets. Over the years, these events promote stenosis and obstruction of blood flow. Known and common risk factors are congenital defects, aging and metabolic syndromes linked to high plasma levels of lipoproteins. Inflammation and oxidative stress are the main molecular mediators of the evolution of aortic stenosis in patients and these mediators regulate both the degradation and remodeling processes. Mitochondrial dysfunction and dysregulation of autophagy also contribute to the disease. A better understanding of these cellular impairments might help to develop new ways to treat patients since, at the moment, there is no effective medical treatment to diminish neither the advancement of valve stenosis nor the left ventricular function impairments, and the current approaches are surgical treatment or transcatheter aortic valve replacement with prosthesis.

RevDate: 2020-11-18
CmpDate: 2020-11-18

Fan L, Wu D, Goremykin V, et al (2020)

Phylogenetic analyses with systematic taxon sampling show that mitochondria branch within Alphaproteobacteria.

Nature ecology & evolution, 4(9):1213-1219.

Though it is well accepted that mitochondria originated from an alphaproteobacteria-like ancestor, the phylogenetic relationship of the mitochondrial endosymbiont to extant Alphaproteobacteria is yet unresolved. The focus of much debate is whether the affinity between mitochondria and fast-evolving alphaproteobacterial lineages reflects true homology or artefacts. Approaches such as site exclusion have been claimed to mitigate compositional heterogeneity between taxa, but this comes at the cost of information loss, and the reliability of such methods is so far unproven. Here we demonstrate that site-exclusion methods produce erratic phylogenetic estimates of mitochondrial origin. Thus, previous phylogenetic hypotheses on the origin of mitochondria based on pretreated datasets should be re-evaluated. We applied alternative strategies to reduce phylogenetic noise by systematic taxon sampling while keeping site substitution information intact. Cross-validation based on a series of trees placed mitochondria robustly within Alphaproteobacteria, sharing an ancient common ancestor with Rickettsiales and currently unclassified marine lineages.

RevDate: 2020-08-02

Fang Y, Zhao C, Xiang H, et al (2020)

Melatonin improves cryopreservation of ram sperm by inhibiting mitochondrial permeability transition pore opening.

Reproduction in domestic animals = Zuchthygiene [Epub ahead of print].

Cryopreservation damages permeability of sperm mitochondrial membranes, with formation of a mitochondrial permeability transition pore (mPTP). Mitochondria are both a primary synthesis site and principle target for melatonin, which can directly inhibit mPTP formation. The objective was to determine effects of melatonin on mPTP opening of frozen-thawed ram sperm and elucidate underlying pathways by antagonist and agonists of melatonin receptors (MTs), and antagonists of PI3K and GSK 3β treatments; furthermore, plasma membrane integrity, mitochondrial membrane potential (ΔΨm), mitochondrial cytochrome c (Cyt c) release and fertilization were analysed to assess the effect of mPTP status mediated by melatonin on quality of frozen-thawed sperm. Fresh ram semen was diluted in glucose-egg yolk buffer with 0 or 10-7 M melatonin (frozen and frozen + melatonin groups, respectively) and slow-frozen. In frozen-thawed sperm, melatonin added at initiation of 4°C equilibration was most effective for inhibiting mPTP opening, decreasing peptidyl-prolyl-cis/trans isomerase activity of cyclophilin D and increasing plasma membrane integrity, ΔΨm, mitochondrial Cyt c concentration and fertilizing ability (p < .05). In a mechanistic study, the melatonin receptor (MT)1 antagonist eliminated inhibition of melatonin on mPTP opening, whereas MT1 agonist had opposite effects (p < .05). Neither MT2 antagonist nor agonist had significant effect, but PI3K and/or GSK 3β antagonist decreased inhibition of MT1 agonist on mPTP opening (p < .05). In conclusion, melatonin improved sperm cryopreservation, perhaps by acting on MT1 via the PI3K-Akt-GSK 3β pathway to inhibit mPTP opening.

RevDate: 2020-09-14
CmpDate: 2020-09-14

de Oliveira VC, Gomes Mariano Junior C, Belizário JE, et al (2020)

Characterization of post-edited cells modified in the TFAM gene by CRISPR/Cas9 technology in the bovine model.

PloS one, 15(7):e0235856.

Gene editing in large animal models for future applications in translational medicine and food production must be deeply investigated for an increase of knowledge. The mitochondrial transcription factor A (TFAM) is a member of the HMGB subfamily that binds to mtDNA promoters. This gene maintains mtDNA, and it is essential for the initiation of mtDNA transcription. Lately, we generated a new cell line through the disruption of the TFAM gene in bovine fibroblast cells by CRISPR/Cas 9 technology. We showed that the CRISPR/Cas9 design was efficient through the generation of heterozygous mutant clones. In this context, once this gene regulates the mtDNA replication specificity, the study aimed to determine if the post-edited cells are capable of in vitro maintenance and assess if they present changes in mtDNA copies and mitochondrial membrane potential after successive passages in culture. The post-edited cells were expanded in culture, and we performed a growth curve, doubling time, cell viability, mitochondrial DNA copy number, and mitochondrial membrane potential assays. The editing process did not make cell culture unfeasible, even though cell growth rate and viability were decreased compared to control since we observed the cells grow well when cultured in a medium supplemented with uridine and pyruvate. They also exhibited a classical fibroblastoid appearance. The RT-qPCR to determine the mtDNA copy number showed a decrease in the edited clones compared to the non-edited ones (control) in different cell passages. Cell staining with Mitotracker Green and red suggests a reduction in red fluorescence in the edited cells compared to the non-edited cells. Thus, through characterization, we demonstrated that the TFAM gene is critical to mitochondrial maintenance due to its interference in the stability of the mitochondrial DNA copy number in different cell passages and membrane potential confirming the decrease in mitochondrial activity in cells edited in heterozygosis.

RevDate: 2020-09-28

Porter SM (2020)

Insights into eukaryogenesis from the fossil record.

Interface focus, 10(4):20190105.

Eukaryogenesis-the process by which the eukaryotic cell emerged-has long puzzled scientists. It has been assumed that the fossil record has little to say about this process, in part because important characters such as the nucleus and mitochondria are rarely preserved, and in part because the prevailing model of early eukaryotes implies that eukaryogenesis occurred before the appearance of the first eukaryotes recognized in the fossil record. Here, I propose a different scenario for early eukaryote evolution than is widely assumed. Rather than crown group eukaryotes originating in the late Paleoproterozoic and remaining ecologically minor components for more than half a billion years in a prokaryote-dominated world, I argue for a late Mesoproterozoic origin of the eukaryotic crown group, implying that eukaryogenesis can be studied using the fossil record. I review the proxy records of four crown group characters: the capacity to form cysts as evidenced by the presence of excystment structures; a complex cytoskeleton as evidenced by spines or pylomes; sterol synthesis as evidenced by steranes; and aerobic respiration-and therefore mitochondria-as evidenced by eukaryotes living in oxic environments, and argue that it might be possible to use these proxy records to infer the order in which these characters evolved. The records indicate that both cyst formation and a complex cytoskeleton appeared by late Paleoproterozoic time, and sterol synthesis appeared in the late Mesoproterozioc or early Neoproterozoic. The origin of aerobic respiration cannot as easily be pinned down, but current evidence permits the possibility that it evolved sometime in the Mesoproterozoic.

RevDate: 2020-09-28

Long X, Xue H, JT Wong (2020)

Descent of Bacteria and Eukarya From an Archaeal Root of Life.

Evolutionary bioinformatics online, 16:1176934320908267.

The 3 biological domains delineated based on small subunit ribosomal RNAs (SSU rRNAs) are confronted by uncertainties regarding the relationship between Archaea and Bacteria, and the origin of Eukarya. The similarities between the paralogous valyl-tRNA and isoleucyl-tRNA synthetases in 5398 species estimated by BLASTP, which decreased from Archaea to Bacteria and further to Eukarya, were consistent with vertical gene transmission from an archaeal root of life close to Methanopyrus kandleri through a Primitive Archaea Cluster to an Ancestral Bacteria Cluster, and to Eukarya. The predominant similarities of the ribosomal proteins (rProts) of eukaryotes toward archaeal rProts relative to bacterial rProts established that an archaeal parent rather than a bacterial parent underwent genome merger with bacteria to generate eukaryotes with mitochondria. Eukaryogenesis benefited from the predominantly archaeal accelerated gene adoption (AGA) phenotype pertaining to horizontally transferred genes from other prokaryotes and expedited genome evolution via both gene-content mutations and nucleotidyl mutations. Archaeons endowed with substantial AGA activity were accordingly favored as candidate archaeal parents. Based on the top similarity bitscores displayed by their proteomes toward the eukaryotic proteomes of Giardia and Trichomonas, and high AGA activity, the Aciduliprofundum archaea were identified as leading candidates of the archaeal parent. The Asgard archaeons and a number of bacterial species were among the foremost potential contributors of eukaryotic-like proteins to Eukarya.

RevDate: 2020-08-11

Gonçalves DJP, Jansen RK, Ruhlman TA, et al (2020)

Under the rug: Abandoning persistent misconceptions that obfuscate organelle evolution.

Molecular phylogenetics and evolution, 151:106903.

The advent and advance of next generation sequencing over the past two decades made it possible to accumulate large quantities of sequence reads that could be used to assemble complete or nearly complete organelle genomes (plastome or mitogenome). The result has been an explosive increase in the availability of organelle genome sequences with over 4000 different species of green plants currently available on GenBank. During the same time period, plant molecular biologists greatly enhanced the understanding of the structure, repair, replication, recombination, transcription and translation, and inheritance of organelle DNA. Unfortunately many plant evolutionary biologists are unaware of or have overlooked this knowledge, resulting in misrepresentation of several phenomena that are critical for phylogenetic and evolutionary studies using organelle genomes. We believe that confronting these misconceptions about organelle genome organization, composition, and inheritance will improve our understanding of the evolutionary processes that underly organelle evolution. Here we discuss four misconceptions that can limit evolutionary biology studies and lead to inaccurate phylogenies and incorrect structure of the organellar DNA used to infer organelle evolution.

RevDate: 2020-09-07

Zhu X, Liu G, Bu Y, et al (2020)

In Situ Monitoring of Mitochondria Regulating Cell Viability by the RNA-Specific Fluorescent Photosensitizer.

Analytical chemistry, 92(15):10815-10821.

Cell viability is greatly affected by external stimulus eliciting correlated dynamical physiological processes for cells to choose survival or death. A few fluorescent probes have been designed to detect whether the cell is in survival state or apoptotic state, but monitoring the regulation process of the cell undergoing survival to death remains a long-standing challenge. Herein, we highlight the in situ monitor of mitochondria regulating the cell viability by the RNA-specific fluorescent photosensitizer L. At normal conditions, L anchored mitochondria and interacted with mito-RNA to light up the mitochondria with red fluorescence. With external light stimulus, L generated reactive oxide species (ROS) and cause damage to mitochondria, which activated mitochondrial autophagy to prevent death, during which the red fluorescence of L witnessed dynamical distribution in accordance with the evolution of vacuole structures containing damaged mitochondria into autophagosomes. However, with ROS continuously increasing, the mitochondrial apoptosis was eventually commenced and L with red fluorescent was gradually accumulated in the nucleoli, indicating the programmed cell death. This work demonstrated how the delicate balance between survival and death are regulated by mitochondria.

RevDate: 2020-09-09
CmpDate: 2020-09-09

Rossi NA, Menchaca-Rodriguez A, Antelo R, et al (2020)

High levels of population genetic differentiation in the American crocodile (Crocodylus acutus).

PloS one, 15(7):e0235288.

The American crocodile (Crocodylus acutus) is a widely distributed species across coastal and brackish areas of the Neotropical region of the Americas and the Greater Antilles. Available information on patterns of genetic differentiation in C. acutus shows a complex structuring influenced by interspecific interactions (mainly hybridization) and anthropogenic actions (mostly historical hunting, recent poaching, habitat loss and fragmentation, and unintentional translocation of individuals). In this study, we used data on mitochondrial DNA control region and 11 nuclear polymorphic microsatellite loci to assess the degree of population structure of C. acutus in South America, North America, Central America and the Greater Antilles. We used traditional genetic differentiation indices, Bayesian clustering and multivariate methods to create a more comprehensive picture of the genetic relationships within the species across its range. Analyses of mtDNA and microsatellite loci show evidence of a strong population genetic structure in the American crocodile, with unique populations in each sampling locality. Our results support previous findings showing large degrees of genetic differentiation between the continental and the Greater Antillean C. acutus. We report three new haplotypes unique to Venezuela, which are considerably less distant from the Central and North American haplotypes than to the Greater Antillean ones. Our findings reveal genetic population differentiation between Cuban and Jamaican C. acutus and offer the first evidence of strong genetic differentiation among the populations of Greater Antillean C. acutus.

RevDate: 2020-09-28

Noiret A, Puch L, Riffaud C, et al (2020)

Sex-Specific Response to Caloric Restriction After Reproductive Investment in Microcebus murinus: An Integrative Approach.

Frontiers in physiology, 11:506.

In seasonal environments, males and females usually maintain high metabolic activity during the whole summer season, exhausting their energy reserves. In the global warming context, unpredictability of food availability during summer could dramatically challenge the energy budget of individuals. Therefore, one can predict that resilience to environmental stress would be dramatically endangered during summer. Here, we hypothesized that females could have greater capacity to survive harsh conditions than males, considering the temporal shift in their respective reproductive energy investment, which can challenge them differently, as well as enhanced flexibility in females' physiological regulation. We tackled this question on the gray mouse lemur (Microcebus murinus), focusing on the late summer period, after the reproductive effort. We monitored six males and six females before and after a 2-weeks 60% caloric restriction (CR), measuring different physiological and cellular parameters in an integrative and comparative multiscale approach. Before CR, females were heavier than males and mostly characterized by high levels of energy expenditure, a more energetic mitochondrial profile and a downregulation of blood antioxidants. We observed a similar energy balance between sexes due to CR, with a decrease in metabolic activity over time only in males. Oxidative damage to DNA was also reduced by different pathways between sexes, which may reflect variability in their physiological status and life-history traits at the end of summer. Finally, females' mitochondria seemed to exhibit greater flexibility and greater metabolic potential than males in response to CR. Our results showed strong differences between males and females in response to food shortage during late summer, underlining the necessity to consider sex as a factor for population dynamics in climate change models.

RevDate: 2020-08-27
CmpDate: 2020-08-25

Keaney TA, Wong HWS, Dowling DK, et al (2020)

Sibling rivalry versus mother's curse: can kin competition facilitate a response to selection on male mitochondria?.

Proceedings. Biological sciences, 287(1930):20200575.

Assuming that fathers never transmit mitochondrial DNA (mtDNA) to their offspring, mitochondrial mutations that affect male fitness are invisible to direct selection on males, leading to an accumulation of male-harming alleles in the mitochondrial genome (mother's curse). However, male phenotypes encoded by mtDNA can still undergo adaptation via kin selection provided that males interact with females carrying related mtDNA, such as their sisters. Here, using experiments with Drosophila melanogaster carrying standardized nuclear DNA but distinct mitochondrial DNA, we test whether the mitochondrial haplotype carried by interacting pairs of larvae affects survival to adulthood, as well as the fitness of the adults. Although mtDNA had no detectable direct or indirect genetic effect on larva-to-adult survival, the fitness of male and female adults was significantly affected by their own mtDNA and the mtDNA carried by their social partner in the larval stage. Thus, mtDNA mutations that alter the effect of male larvae on nearby female larvae (which often carry the same mutation, due to kinship) could theoretically respond to kin selection. We discuss the implications of our findings for the evolution of mitochondria and other maternally inherited endosymbionts.

RevDate: 2020-09-21
CmpDate: 2020-09-21

Wu Z, Waneka G, Broz AK, et al (2020)

MSH1 is required for maintenance of the low mutation rates in plant mitochondrial and plastid genomes.

Proceedings of the National Academy of Sciences of the United States of America, 117(28):16448-16455.

Mitochondrial and plastid genomes in land plants exhibit some of the slowest rates of sequence evolution observed in any eukaryotic genome, suggesting an exceptional ability to prevent or correct mutations. However, the mechanisms responsible for this extreme fidelity remain unclear. We tested seven candidate genes involved in cytoplasmic DNA replication, recombination, and repair (POLIA, POLIB, MSH1, RECA3, UNG, FPG, and OGG1) for effects on mutation rates in the model angiosperm Arabidopsis thaliana by applying a highly accurate DNA sequencing technique (duplex sequencing) that can detect newly arisen mitochondrial and plastid mutations even at low heteroplasmic frequencies. We find that disrupting MSH1 (but not the other candidate genes) leads to massive increases in the frequency of point mutations and small indels and changes to the mutation spectrum in mitochondrial and plastid DNA. We also used droplet digital PCR to show transmission of de novo heteroplasmies across generations in msh1 mutants, confirming a contribution to heritable mutation rates. This dual-targeted gene is part of an enigmatic lineage within the mutS mismatch repair family that we find is also present outside of green plants in multiple eukaryotic groups (stramenopiles, alveolates, haptophytes, and cryptomonads), as well as certain bacteria and viruses. MSH1 has previously been shown to limit ectopic recombination in plant cytoplasmic genomes. Our results point to a broader role in recognition and correction of errors in plant mitochondrial and plastid DNA sequence, leading to greatly suppressed mutation rates perhaps via initiation of double-stranded breaks and repair pathways based on faithful homologous recombination.

RevDate: 2020-09-21
CmpDate: 2020-09-21

Greenway R, Barts N, Henpita C, et al (2020)

Convergent evolution of conserved mitochondrial pathways underlies repeated adaptation to extreme environments.

Proceedings of the National Academy of Sciences of the United States of America, 117(28):16424-16430.

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H2S)-a toxicant that impairs mitochondrial function-across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H2S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H2S in sulfide spring P. mexicana but not ancestral lineages from nonsulfidic habitats due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H2S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. On a macroevolutionary scale, H2S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes in genes associated with H2S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and-in some instances-codons are implicated in H2S adaptation in lineages that span 40 million years of evolution.

RevDate: 2020-09-28

Mannella CA (2020)

Consequences of Folding the Mitochondrial Inner Membrane.

Frontiers in physiology, 11:536.

A fundamental first step in the evolution of eukaryotes was infolding of the chemiosmotic membrane of the endosymbiont. This allowed the proto-eukaryote to amplify ATP generation while constraining the volume dedicated to energy production. In mitochondria, folding of the inner membrane has evolved into a highly regulated process that creates specialized compartments (cristae) tuned to optimize function. Internalizing the inner membrane also presents complications in terms of generating the folds and maintaining mitochondrial integrity in response to stresses. This review describes mechanisms that have evolved to regulate inner membrane topology and either preserve or (when appropriate) rupture the outer membrane.

RevDate: 2020-09-02

Nesci S, Pagliarani A, Algieri C, et al (2020)

Mitochondrial F-type ATP synthase: multiple enzyme functions revealed by the membrane-embedded FO structure.

Critical reviews in biochemistry and molecular biology, 55(4):309-321.

Of the two main sectors of the F-type ATP synthase, the membrane-intrinsic FO domain is the one which, during evolution, has undergone the highest structural variations and changes in subunit composition. The FO complexity in mitochondria is apparently related to additional enzyme functions that lack in bacterial and thylakoid complexes. Indeed, the F-type ATP synthase has the main bioenergetic role to synthesize ATP by exploiting the electrochemical gradient built by respiratory complexes. The FO membrane domain, essential in the enzyme machinery, also participates in the bioenergetic cost of synthesizing ATP and in the formation of the cristae, thus contributing to mitochondrial morphology. The recent enzyme involvement in a high-conductance channel, which forms in the inner mitochondrial membrane and promotes the mitochondrial permeability transition, highlights a new F-type ATP synthase role. Point mutations which cause amino acid substitutions in FO subunits produce mitochondrial dysfunctions and lead to severe pathologies. The FO variability in different species, pointed out by cryo-EM analysis, mirrors the multiple enzyme functions and opens a new scenario in mitochondrial biology.

RevDate: 2020-09-02
CmpDate: 2020-09-02

Pyrih J, Rašková V, Škodová-Sveráková I, et al (2020)

ZapE/Afg1 interacts with Oxa1 and its depletion causes a multifaceted phenotype.

PloS one, 15(6):e0234918.

ZapE/Afg1 is a component of the inner cell membrane of some eubacteria and the inner mitochondrial membrane of eukaryotes. This protein is involved in FtsZ-dependent division of eubacteria. In the yeast and human mitochondrion, ZapE/Afg1 likely interacts with Oxa1 and facilitates the degradation of mitochondrion-encoded subunits of respiratory complexes. Furthermore, the depletion of ZapE increases resistance to apoptosis, decreases oxidative stress tolerance, and impacts mitochondrial protein homeostasis. It remains unclear whether ZapE is a multifunctional protein, or whether some of the described effects are just secondary phenotypes. Here, we have analyzed the functions of ZapE in Trypanosoma brucei, a parasitic protist, and an important model organism. Using a newly developed proximity-dependent biotinylation approach (BioID2), we have identified the inner mitochondrial membrane insertase Oxa1 among three putative interacting partners of ZapE, which is present in two paralogs. RNAi-mediated depletion of both ZapE paralogs likely affected the function of respiratory complexes I and IV. Consistently, we show that the distribution of mitochondrial ZapE is restricted only to organisms with Oxa1, respiratory complexes, and a mitochondrial genome. We propose that the evolutionarily conserved interaction of ZapE with Oxa1, which is required for proper insertion of many inner mitochondrial membrane proteins, is behind the multifaceted phenotype caused by the ablation of ZapE.

RevDate: 2020-06-22

Levitskii SA, Baleva MV, Chicherin IV, et al (2020)

Protein Biosynthesis in Mitochondria: Past Simple, Present Perfect, Future Indefinite.

Biochemistry. Biokhimiia, 85(3):257-263.

Mitochondria are obligate organelles of most eukaryotic cells that perform many different functions important for cellular homeostasis. The main role of mitochondria is supplying cells with energy in a form of ATP, which is synthesized in a chain of oxidative phosphorylation reactions on the organelle inner membrane. It is commonly believed now that mitochondria have the endosymbiotic origin. In the course of evolution, they have lost most of their genetic material as a result of genome reduction and gene transfer to the nucleus. The majority of mitochondrial proteins are synthesized in the cytosol and then imported to the mitochondria. However, almost all known mitochondria still contain genomes that are maintained and expressed. The processes of protein biosynthesis in the mitochondria - mitochondrial translation - substantially differs from the analogous processes in bacteria and the cytosol of eukaryotic cells. Mitochondrial translation is characterized by a high degree of specialization and specific regulatory mechanisms. In this review, we analyze available information on the common principles of mitochondrial translation with emphasis on the molecular mechanisms of translation initiation in the mitochondria of yeast and mammalian cells.

RevDate: 2020-08-24
CmpDate: 2020-08-24

Nong W, Cao J, Li Y, et al (2020)

Jellyfish genomes reveal distinct homeobox gene clusters and conservation of small RNA processing.

Nature communications, 11(1):3051 pii:10.1038/s41467-020-16801-9.

The phylum Cnidaria represents a close outgroup to Bilateria and includes familiar animals including sea anemones, corals, hydroids, and jellyfish. Here we report genome sequencing and assembly for true jellyfish Sanderia malayensis and Rhopilema esculentum. The homeobox gene clusters are characterised by interdigitation of Hox, NK, and Hox-like genes revealing an alternate pathway of ANTP class gene dispersal and an intact three gene ParaHox cluster. The mitochondrial genomes are linear but, unlike in Hydra, we do not detect nuclear copies, suggesting that linear plastid genomes are not necessarily prone to integration. Genes for sesquiterpenoid hormone production, typical for arthropods, are also now found in cnidarians. Somatic and germline cells both express piwi-interacting RNAs in jellyfish revealing a conserved cnidarian feature, and evidence for tissue-specific microRNA arm switching as found in Bilateria is detected. Jellyfish genomes reveal a mosaic of conserved and divergent genomic characters evolved from a shared ancestral genetic architecture.

RevDate: 2020-07-14

Tobiasson V, A Amunts (2020)

Ciliate mitoribosome illuminates evolutionary steps of mitochondrial translation.

eLife, 9:.

To understand the steps involved in the evolution of translation, we used Tetrahymena thermophila, a ciliate with high coding capacity of the mitochondrial genome, as the model organism and characterized its mitochondrial ribosome (mitoribosome) using cryo-EM. The structure of the mitoribosome reveals an assembly of 94-ribosomal proteins and four-rRNAs with an additional protein mass of ~700 kDa on the small subunit, while the large subunit lacks 5S rRNA. The structure also shows that the small subunit head is constrained, tRNA binding sites are formed by mitochondria-specific protein elements, conserved protein bS1 is excluded, and bacterial RNA polymerase binding site is blocked. We provide evidence for anintrinsic protein targeting system through visualization of mitochondria-specific mL105 by the exit tunnel that would facilitate the recruitment of a nascent polypeptide. Functional protein uS3m is encoded by three complementary genes from the nucleus and mitochondrion, establishing a link between genetic drift and mitochondrial translation. Finally, we reannotated nine open reading frames in the mitochondrial genome that code for mitoribosomal proteins.

RevDate: 2020-09-28

Timón-Gómez A, A Barrientos (2020)

Mitochondrial respiratory chain composition and organization in response to changing oxygen levels.

Journal of life sciences (Westlake Village, Calif.), 2(2):.

Mitochondria are the major consumer of oxygen in eukaryotic cells, owing to the requirement of oxygen to generate ATP through the mitochondrial respiratory chain (MRC) and the oxidative phosphorylation system (OXPHOS). This aerobic energy transduction is more efficient than anaerobic processes such as glycolysis. Hypoxia, a condition in which environmental or intracellular oxygen levels are below the standard range, triggers an adaptive signaling pathway within the cell. When oxygen concentrations are low, hypoxia-inducible factors (HIFs) become stabilized and activated to mount a transcriptional response that triggers modulation of cellular metabolism to adjust to hypoxic conditions. Mitochondrial aerobic metabolism is one of the main targets of the hypoxic response to regulate its functioning and efficiency in the presence of decreased oxygen levels. During evolution, eukaryotic cells and tissues have increased the plasticity of their mitochondrial OXPHOS system to cope with metabolic needs in different oxygen contexts. In mammalian mitochondria, two factors contribute to this plasticity. First, several subunits of the multimeric MRC complexes I and IV exist in multiple tissue-specific and condition-specific isoforms. Second, the MRC enzymes can coexist organized as individual entities or forming supramolecular structures known as supercomplexes, perhaps in a dynamic manner to respond to environmental conditions and cellular metabolic demands. In this review, we will summarize the information currently available on oxygen-related changes in MRC composition and organization and will discuss gaps of knowledge and research opportunities in the field.

RevDate: 2020-09-28

Monteiro LB, Davanzo GG, de Aguiar CF, et al (2020)

Using flow cytometry for mitochondrial assays.

MethodsX, 7:100938.

The understanding of how different cell types adapt their metabolism in the face of challenges has been attracting the attention of researchers for many years. Recently, immunologists also started to focus on how the metabolism of immune cells can impact the way that immunity drives its responses. The presence of a pathogen or damage in a tissue changes severely the way that the immune cells need to respond. When activated, immune cells usually shift their metabolism from a high energy demanding status using mitochondria respiration to a glycolytic based rapid ATP production. The diminished amount of respiration leads to changes in the mitochondrial membrane potential and, consequently, generation of reactive oxygen species. Here, we show how flow cytometry can be used to track changes in mitochondrial mass, membrane potential and superoxide (ROS) production in live immune cells. ● This protocol suggests a quick way of evaluating mitochondrial fitness using flow cytometry. We propose using the probes MitoTraker Green and MitoTracker Red/ MitoSOX at the same time. This way, it is possible to evaluate different parameters of mitochondrial biology in living cells. ● Flow cytometry is a highly used tool by immunologists. With the advances of studies focusing on the metabolism of immune cells, a simplified application of flow cytometry for mitochondrial studies and screenings is a helpful clarifying method for immunology.

RevDate: 2020-07-23

Valero C, Colabardini AC, Chiaratto J, et al (2020)

Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect.

mBio, 11(3):.

Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in A. fumigatus and new strategies are needed to combat invasive aspergillosis. Caspofungin is effective against other human-pathogenic fungal species, but it is fungistatic only against A. fumigatus Resistance to caspofungin in A. fumigatus has been linked to mutations in the fksA gene that encodes the target enzyme of the drug β-1,3-glucan synthase. However, tolerance of high caspofungin concentrations, a phenomenon known as the caspofungin paradoxical effect (CPE), is also important for subsequent adaptation and drug resistance evolution. Here, we identified and characterized the transcription factors involved in the response to CPE by screening an A. fumigatus library of 484 null transcription factors (TFs) in CPE drug concentrations. We identified 11 TFs that had reduced CPE and that encoded proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism, and cell wall remodeling. One of these TFs, FhdA, was important for mitochondrial respiratory function and iron metabolism. The ΔfhdA mutant showed decreased growth when exposed to Congo red or to high temperature. Transcriptome sequencing (RNA-seq) analysis and further experimental validation indicated that the ΔfhdA mutant showed diminished respiratory capacity, probably affecting several pathways related to the caspofungin tolerance and resistance. Our results provide the foundation to understand signaling pathways that are important for caspofungin tolerance and resistance.IMPORTANCEAspergillus fumigatus, one of the most important human-pathogenic fungal species, is able to cause aspergillosis, a heterogeneous group of diseases that presents a wide range of clinical manifestations. Invasive pulmonary aspergillosis is the most serious pathology in terms of patient outcome and treatment, with a high mortality rate ranging from 50% to 95% primarily affecting immunocompromised patients. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, there were several reports of evolution of clinical azole resistance in the last decade. Caspofungin, a noncompetitive β-1,3-glucan synthase inhibitor, has been used against A. fumigatus, but it is fungistatic and is recommended as second-line therapy for invasive aspergillosis. More information about caspofungin tolerance and resistance is necessary in order to refine antifungal strategies that target the fungal cell wall. Here, we screened a transcription factor (TF) deletion library for TFs that can mediate caspofungin tolerance and resistance. We have identified 11 TFs that are important for caspofungin sensitivity and/or for the caspofungin paradoxical effect (CPE). These TFs encode proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism or cell wall remodeling, and mitochondrial respiratory function. The study of those genes regulated by TFs identified in this work will provide a better understanding of the signaling pathways that are important for caspofungin tolerance and resistance.

RevDate: 2020-10-06
CmpDate: 2020-10-06

Li Y, Nourbakhsh N, Pham H, et al (2020)

Evolution of altered tubular metabolism and mitochondrial function in sepsis-associated acute kidney injury.

American journal of physiology. Renal physiology, 319(2):F229-F244.

Sepsis-associated acute kidney injury (s-AKI) has a staggering impact in patients and lacks any treatment. Incomplete understanding of the pathogenesis of s-AKI is a major barrier to the development of effective therapies. We address the gaps in knowledge regarding renal oxygenation, tubular metabolism, and mitochondrial function in the pathogenesis of s-AKI using the cecal ligation and puncture (CLP) model in mice. At 24 h after CLP, renal oxygen delivery was reduced; however, fractional oxygen extraction was unchanged, suggesting inefficient renal oxygen utilization despite decreased glomerular filtration rate and filtered load. To investigate the underlying mechanisms, we examined temporal changes in mitochondrial function and metabolism at 4 and 24 h after CLP. At 4 h after CLP, markers of mitochondrial content and biogenesis were increased in CLP kidneys, but mitochondrial oxygen consumption rates were suppressed in proximal tubules. Interestingly, at 24 h, proximal tubular mitochondria displayed high respiratory capacity, but with decreased mitochondrial content, biogenesis, fusion, and ATP levels in CLP kidneys, suggesting decreased ATP synthesis efficiency. We further investigated metabolic reprogramming after CLP and observed reduced expression of fatty acid oxidation enzymes but increased expression of glycolytic enzymes at 24 h. However, assessment of functional glycolysis revealed lower glycolytic capacity, glycolytic reserve, and compensatory glycolysis in CLP proximal tubules, which may explain their susceptibility to injury. In conclusion, we demonstrated significant alterations in renal oxygenation, tubular mitochondrial function, and metabolic reprogramming in s-AKI, which may play an important role in the progression of injury and recovery from AKI in sepsis.

RevDate: 2020-11-16
CmpDate: 2020-11-16

Mao X, SJ Rossiter (2020)

Genome-wide data reveal discordant mitonuclear introgression in the intermediate horseshoe bat (Rhinolophus affinis).

Molecular phylogenetics and evolution, 150:106886.

Closely related taxa often exhibit mitonuclear discordance attributed to introgression of mitochondrial DNA (mtDNA), yet few studies have considered the underlying causes of mtDNA introgression. Here we test for demographic versus adaptive processes as explanations for mtDNA introgression in three subspecies of the intermediate horseshoe bat (Rhinolophus affinis). We generated sequences of 1692 nuclear genes and 13 mitochondrial protein-coding genes for 48 individuals. Phylogenetic reconstructions based on 320 exon sequences and 2217 single nucleotide polymorphisms (SNPs) both revealed conflicts between the species tree and mtDNA tree. These results, together with geographic patterns of mitonuclear discordance, and shared identical or near-identical mtDNA sequences, suggest extensive introgression of mtDNA between the two parapatric mainland subspecies. Under demographic hypotheses, we would also expect to uncover traces of ncDNA introgression, however, population structure and gene flow analyses revealed little nuclear admixture. Furthermore, we found inconsistent estimates of the timing of population expansion and that of the most recent common ancestor for the clade containing introgressed haplotypes. Without a clear demographic explanation, we also examined whether introgression likely arises from adaptation. We found that five mtDNA genes contained fixed amino acid differences between introgressed and non-introgressed individuals, including putative positive selection found in one codon, although this did not show introgression. While our evidence for rejecting demographic hypotheses is arguably stronger than that for rejecting adaptation, we find no definitive support for either explanation. Future efforts will focus on larger-scale resequencing to decipher the underlying causes of discordant mitonuclear introgression in this system.

RevDate: 2020-11-16
CmpDate: 2020-11-16

Pozzi L, Penna A, Bearder SK, et al (2020)

Cryptic diversity and species boundaries within the Paragalago zanzibaricus species complex.

Molecular phylogenetics and evolution, 150:106887.

The recently described genus Paragalago is a complex of several nocturnal and morphologically cryptic species distributed in the forests of eastern Africa. Species diversity within this genus has been mainly described using species-specific differences in their loud calls. However, molecular data are still lacking for this group and species boundaries remain unclear. In this study, we explore species diversity within the zanzibaricus-complex using a combination of mitochondrial and nuclear data and comparing multiple species delimitation methods. Our results consistently support the existence of three independent lineages, P. cocos, P. zanzibaricus, and P. granti, confirming previous hypotheses based on vocal data. We conclude that these three lineages represent valid cryptic species and we hypothesize that speciation within this complex was characterized by cycles of forest expansion and contraction in the Plio-Pleistocene.

RevDate: 2020-11-05

Vertika S, Singh KK, S Rajender (2020)

Mitochondria, spermatogenesis, and male infertility - An update.

Mitochondrion, 54:26-40.

The incorporation of mitochondria in the eukaryotic cell is one of the most enigmatic events in the course of evolution. This important organelle was thought to be only the powerhouse of the cell, but was later learnt to perform many other indispensable functions in the cell. Two major contributions of mitochondria in spermatogenesis concern energy production and apoptosis. Apart from this, mitochondria also participate in a number of other processes affecting spermatogenesis and fertility. Mitochondria in sperm are arranged in the periphery of the tail microtubules to serve to energy demand for motility. Apart from this, the role of mitochondria in germ cell proliferation, mitotic regulation, and the elimination of germ cells by apoptosis are now well recognized. Eventually, mutations in the mitochondrial genome have been reported in male infertility, particularly in sluggish sperm (asthenozoospermia); however, heteroplasmy in the mtDNA and a complex interplay between the nucleus and mitochondria affect their penetrance. In this article, we have provided an update on the role of mitochondria in various events of spermatogenesis and male fertility and on the correlation of mitochondrial DNA mutations with male infertility.

RevDate: 2020-06-10

Enomoto H, Mittal N, Inomata T, et al (2020)

Dilated Cardiomyopathy (DCM)-linked Heat shock protein Family D Member 1 (HSPD1) mutations cause upregulation of ROS and autophagy through mitochondrial dysfunction.

Cardiovascular research pii:5855671 [Epub ahead of print].

BACKGROUND: During heart failure, the levels of circulatory HSPD1 (HSP60) increase. However, its underlying mechanism is still unknown. The apical domain of HSPD1 is conserved throughout evolution. We found a point mutation in HSPD1 in a familial dilated cardiomyopathy (DCM) patient. A similar point mutation in HSPD1 in the zebrafish mutant, nbl, led to loss of its regenerative capacity and development of pericardial edema under heat stress condition. In this study, we aimed to determine the direct involvement of HSPD1 in the development of DCM.

METHODS AND RESULTS: By Sanger method, we found a point mutation (Thr320Ala) in the apical domain of HSPD1, in one familial DCM patient, which was four amino acids away from the point mutation (Val324Glu) in the nbl mutant zebrafish. The nbl mutants showed atrioventricular block and sudden death at eight months post-fertilization. Histological and microscopic analysis of the nbl mutant hearts showed decreased ventricular wall thickness, elevated level of reactive oxygen species (ROS), increased fibrosis, mitochondrial damage, and increased autophagosomes. mRNA and protein expression of autophagy-related genes significantly increased in nbl mutants. We established HEK293 stable cell lines of WT, nbl-type, and DCM-type HSPD1, with tetracycline-dependent expression. Compared to WT, both nbl- and DCM-type cells showed decreased cell growth, increased expression of ROS and autophagy-related genes, inhibition of the activity of mitochondrial electron transport chain complexes III and IV, and decreased mitochondrial fission and fusion.

CONCLUSIONS: Mutations in HSPD1 caused mitochondrial dysfunction and induced mitophagy. Mitochondrial dysfunction caused increased ROS and cardiac atrophy.

TRANSLATIONAL PERSPECTIVE: The aged heart is more susceptible to stress despite the increased compensatory chaperones/co-chaperones activity. Here, we identified a point mutation in HSPD1 in a human DCM family. Using zebrafish, we demonstrated that functional inactivation of HSPD1 resulted in increased ROS level and mitophagy, thereby resulting in heart failure at a relatively early age. Inhibition of ROS activity by antioxidants decreased cell death and mitophagy. This work identifies the key role of HSPD1 in cardiac muscle protection and suggests the supplementation of antioxidants may improve the cardiac function through the mitochondrial ROS pathway in patients with chronic heart failure.

RevDate: 2020-11-16
CmpDate: 2020-11-16

Sun S, Li Q, Kong L, et al (2020)

Evolution of mitochondrial gene arrangements in Arcidae (Bivalvia: Arcida) and their phylogenetic implications.

Molecular phylogenetics and evolution, 150:106879.

Arcidae is a diverse group of ark shells with over 260 described species. The phylogenetic relationships and the evolution of the mitochondrial genomes in this family were poorly understood. Comparisons of mitogenomes have been widely used to explore the phylogenetic relationship among animal taxa. We described the complete mitogenomes of Arca navicularis, Scapharca gubernaculum and one nearly complete mitogenome of Anadara consociata. The mitogenome of A. navicularis (18,103 bp) is currently the smallest known Arcidae mitogenome, while the mitogenomes of S. gubernaculum (45,697 bp) and A. consociata (44,034 bp) are relatively large. The mitochondrial gene orders of the three taxa were substantially different from each other, as well as the patterns found in other ark shells. The relationships among Arcidae species recovered from different mitochondrial characters (nucleotide sequence versus gene order) were in disagreement. The phylogeny based on nucleotide sequences did not support the monophyly of Arcidae, as Cucullaea labiata (Cucullaeidae) appeared as a subgroup within Arcinae, rather than sister group to the family Arcidae. In addition, we presented the first time-calibrated evolutionary tree of Arcidae based on mitochondrial DNA (mtDNA) sequences, which placed the deepest divergence within Arcidae at 342.36 million years ago (Mya), around the Carboniferous (360-300 Mya).


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
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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 )