Alternative splicing of COQ-2 determines the choice between ubiquinone and rhodoquinone biosynthesis in helminths

Jh, Tan; Lautens, Margot; Romanelli-Cedrez, Laura; Wang, Jianbin; Schertzberg, Michael R; Reinl, Samantha R.; Davis, Richard E.; Shepherd, Jennifer; Fraser, Andrew G.; Salinas, Gustavo

doi:10.1101/2020.02.28.965087

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…The fumarate reduction during anaerobic energy metabolism in eukaryotes is usually associated with rhodoquinone (RQ) as an electron carrier, and RQ generally replaces ubiquinone as an electron carrier in the electron transport chain after the switch from aerobic metabolism to anaerobic metabolism [35]. The switch to RQ synthesis during anaerobic metabolism is controlled by the polyprenyltransferase COQ-2 [35], but we could not find any expressed ORFs in our metatranscriptomes with significant similarity to this gene. Future controlled experiments involving the switch from anaerobic conditions could test whether Foraminifera indeed use RQ as an electron carrier during anaerobic energy metabolism.…”

Section: Discussionmentioning

confidence: 77%

Anaerobic metabolism of Foraminifera thriving below the seafloor

et al. 2020

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Foraminifera are single-celled eukaryotes (protists) of large ecological importance, as well as environmental and paleoenvironmental indicators and biostratigraphic tools. In addition, they are capable of surviving in anoxic marine environments where they represent a major component of the benthic community. However, the cellular adaptations of Foraminifera to the anoxic environment remain poorly constrained. We sampled an oxic-anoxic transition zone in marine sediments from the Namibian shelf, where the genera Bolivina and Stainforthia dominated the Foraminifera community, and use metatranscriptomics to characterize Foraminifera metabolism across the different geochemical conditions. Relative Foraminifera gene expression in anoxic sediment increased an order of magnitude, which was confirmed in a 10-day incubation experiment where the development of anoxia coincided with a 20–40-fold increase in the relative abundance of Foraminifera protein encoding transcripts, attributed primarily to those involved in protein synthesis, intracellular protein trafficking, and modification of the cytoskeleton. This indicated that many Foraminifera were not only surviving but thriving, under the anoxic conditions. The anaerobic energy metabolism of these active Foraminifera was characterized by fermentation of sugars and amino acids, fumarate reduction, and potentially dissimilatory nitrate reduction. Moreover, the gene expression data indicate that under anoxia Foraminifera use the phosphogen creatine phosphate as an ATP store, allowing reserves of high-energy phosphate pool to be maintained for sudden demands of increased energy during anaerobic metabolism. This was co-expressed alongside genes involved in phagocytosis and clathrin-mediated endocytosis (CME). Foraminifera may use CME to utilize dissolved organic matter as a carbon and energy source, in addition to ingestion of prey cells via phagocytosis. These anaerobic metabolic mechanisms help to explain the ecological success of Foraminifera documented in the fossil record since the Cambrian period more than 500 million years ago.

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Section: Discussionmentioning

confidence: 77%

Anaerobic metabolism of Foraminifera thriving below the seafloor

et al. 2020

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“…Within the Caenorhabditis genus, some species, like C. elegans, encode an alanine at COI position 153, while others, including C. afra, encode serine at the same position (Table S6). Several nematodes, including Caenorhabditis worms, can synthesize either ubiquinone, associated with aerobic environments, or rhodoquinone, associated with anaerobic metabolism (Takamiya et al 1999;Del Borrello et al 2019;Tan et al 2020). These findings suggest that these organisms also encounter fluctuating oxygen concentrations, prompting further speculation that changes to position 153 are linked to oxygen availability or consumption.…”

Section: Resultsmentioning

confidence: 99%

An Unusual Amino Acid Substitution Within Hummingbird CytochromecOxidase Alters a Key Proton-Conducting Channel

Dunn

Akpınar

Sharma

2020

G3 Genes|Genomes|Genetics

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Hummingbirds in flight exhibit the highest mass-specific metabolic rate of all vertebrates. The bioenergetic requirements associated with sustained hovering flight raise the possibility of unique amino acid substitutions that would enhance aerobic metabolism. Here, we have identified a non-conservative substitution within the mitochondria-encoded cytochrome c oxidase subunit I (COI) that is fixed within hummingbirds, but not among other vertebrates. This unusual change is also rare among metazoans, but can be identified in several clades with diverse life histories. We performed atomistic molecular dynamics simulations using bovine and hummingbird COI models, thereby bypassing experimental limitations imposed by the inability to modify mtDNA in a site-specific manner. Intriguingly, our findings suggest that COI amino acid position 153 (bovine numbering convention) provides control over the hydration and activity of a key proton channel in COX. We discuss potential phenotypic outcomes linked to this alteration encoded by hummingbird mitochondrial genomes.

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Section: Rq Is Essential For Survival In Sulfidementioning

confidence: 99%

“…COQ-2 is essential for RQ and UQ biosynthesis (45). Organisms that synthesize RQ possess two isoforms of this enzyme (COQ-2A and COQ-2E), derived from mutually exclusive alternative splicing (45). COQ-2E, which is absent in organisms that do not synthesize RQ, has been shown to be essential for RQ biosynthesis.…”

Section: Rq Is Essential For Survival In Sulfidementioning

confidence: 99%

Rhodoquinone-dependent electron transport chain is essential forC. eleganssurvival in hydrogen sulfide environments

Romanelli-Cedrez,

vairoletti,

Salinas

2024

Preprint

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Hydrogen sulfide (H2S) has traditionally been considered as an environmental toxin for animal lineages; yet, it plays a signaling role in various processes at low concentrations. Mechanisms controlling H2S in animals, especially in sulfide-rich environments, are not fully understood. The main detoxification pathway involves the conversion of H2S into less harmful forms, through a mitochondrial oxidation pathway. The first step of this pathway oxidizes sulfide and reduces ubiquinone (UQ) through sulfide-quinone oxidoreductase (SQRD/SQOR). Because H2S inhibits cytochrome oxidase and hence UQ regeneration, this pathway becomes compromised at high H2S concentrations. The free-living nematodeC. elegansfeeds on bacteria and can face high sulfide concentrations in its natural environment. This organism has an alternative ETC that uses rhodoquinone (RQ) as the lipidic electron transporter and fumarate as the final electron acceptor. In this study, we demonstrate that RQ is essential for survival in sulfide. RQ-less animals (kynu-1andcoq-2eKO) cannot survive high H2S concentrations, while UQ-less animals (clk-1andcoq-2aKO) exhibit recovery, even when provided with a UQ-deficient diet. Our findings highlight thatsqrd-1uses both benzoquinones and that RQ-dependent ETC confers a key advantage (RQ regeneration) over UQ in sulfide conditions.C. elegansalso faces cyanide, another cytochrome oxidase inhibitor, whose detoxification leads to H2S production, viacysl-2. Our study reveals that RQ delays killing by the HCN-producing bacteriaPseudomonas aeruginosaPAO1. These results underscore the fundamental role that RQ-dependent ETC serves as a biochemical adaptation to H2S environments, and to pathogenic bacteria producing cyanide and H2S toxins.

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Alternative splicing of COQ-2 determines the choice between ubiquinone and rhodoquinone biosynthesis in helminths

Cited by 4 publications

References 42 publications

Anaerobic metabolism of Foraminifera thriving below the seafloor

Anaerobic metabolism of Foraminifera thriving below the seafloor

An Unusual Amino Acid Substitution Within Hummingbird CytochromecOxidase Alters a Key Proton-Conducting Channel

Rhodoquinone-dependent electron transport chain is essential forC. eleganssurvival in hydrogen sulfide environments

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