ArticleCell2024
Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism.
Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 29 citations in OpenAlex.
- A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Modulating Ubiquinone Biosynthesis Rescues Mitochondrial Dysfunction by Genetic Interaction in a Phosphatidylethanolamine (PE)-Deficient Disease Model.Antioxidants (Basel, Switzerland) · 2026Article
- InsP3R signaling and actomyosin-dependent mitochondrial dynamics play essential roles in mitochondrial stress-induced longevity.Nature communications · 2026Article
- A novel multisystem approach uncovers conserved mitochondrial complex I disease phenotypes and suppressors.Research square · 2026Article
- Drug development targeting the mitochondrial respiratory chain of Sparganum proliferum: Initial biochemical and drug discovery insights into the enigmatic helminth parasite.PLoS neglected tropical diseases · 2026Article
- Hypoxia rescues complex 1-associated disease caused by proteostatic defects.Nature metabolism · 2026Article
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 2026Review
- 4,5-dihydroxyhexanoic acid is a robust circulating and urine marker of mitochondrial disease and its severity.bioRxiv : the preprint server for biology · 2026Article
- Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.Investigative ophthalmology & visual science · 2026Article
- Suppressive Genetic Interactions Between Haploinsufficient Mitochondrial Genes Encoded in the 22q11.2 Microdeletion Locus Define Brain and Cardiac Phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Article
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Abundant Recurrent Mitochondrial Mutations and Widespread Mitonuclear Epistasis in Caenorhabditis elegans.Molecular biology and evolution · 2025Article
- The mitochondrial trans-2-enoyl-CoA reductase is necessary for mitochondrial homeostasis in C. elegans.Genetics · 2025Article
- InsP3R signaling mediates mitochondrial stress-induced longevity through actomyosin-dependent mitochondrial dynamics.bioRxiv : the preprint server for biology · 2025Article
- Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease.Nature neuroscience · 2025Article
- Mitochondrial Reverse Electron Transport: Mechanisms, Pathophysiological Roles, and Therapeutic Potential.Biology · 2025Review
- Respiratory complex IIIbioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The electron transport chain (ETC) of mitochondria, bacteria, and archaea couples electron flow to proton pumping and is adapted to diverse oxygen environments. Remarkably, in mice, neurological disease due to ETC complex I dysfunction is rescued by hypoxia through unknown mechanisms. Here, we show that hypoxia rescue and hyperoxia sensitivity of complex I deficiency are evolutionarily conserved to C. elegans and are specific to mutants that compromise the electron-conducting matrix arm. We show that hypoxia rescue does not involve the hypoxia-inducible factor pathway or attenuation of reactive oxygen species. To discover the mechanism, we use C. elegans genetic screens to identify suppressor mutations in the complex I accessory subunit NDUFA6/nuo-3 that phenocopy hypoxia rescue. We show that NDUFA6/nuo-3(G60D) or hypoxia directly restores complex I forward activity, with downstream rescue of ETC flux and, in some cases, complex I levels. Additional screens identify residues within the ubiquinone binding pocket as being required for the rescue by NDUFA6/nuo-3(G60D) or hypoxia. This reveals oxygen-sensitive coupling between an accessory subunit and the quinone binding pocket of complex I that can restore forward activity in the same manner as hypoxia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.