ArticlePLoS genetics2013
Alternative oxidase expression in the mouse enables bypassing cytochrome c oxidase blockade and limits mitochondrial ROS overproduction.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 116 citations in OpenAlex.
- Analysis of Short-Term Responses to Hypoxia During Stirred-Tank Fermentation inJournal of fungi (Basel, Switzerland) · 2026Article
- Mitochondrial ROS and HIF-1α signaling mediate synaptic plasticity in the critical period.PLoS biology · 2025Article
- Article
- Impairment of Muscle Function Causes Pupal Lethality in Flies Expressing the Mitochondrial Alternative Oxidase.Biomolecules · 2025Article
- Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases.Science advances · 2025Review
- Alternative oxidase blunts pseudohypoxia and photoreceptor degeneration due to RPE mitochondrial dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- From Beach to the Bedside: Harnessing Mitochondrial Function in Human Diseases Using New Marine-Derived Strategies.International journal of molecular sciences · 2024Review
- Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models.International journal of molecular sciences · 2023Review
- Alternative oxidase causes cell type- and tissue-specific responses in mutator mice.Life science alliance · 2023Article
- Alternative oxidase encoded by sequence-optimized and chemically-modified RNA transfected into mammalian cells is catalytically active.Gene therapy · 2022Article
- Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?The Biochemical journal · 2022Review
- Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation.Nature immunology · 2022Article
- Characterization of a highly diverged mitochondrial ATP synthase FThe Journal of biological chemistry · 2022Article
- Regulation of neuronal bioenergetics as a therapeutic strategy in neurodegenerative diseases.Neural regeneration research · 2021Article
- Production and scavenging of reactive oxygen species both affect reproductive success in male and female Drosophila melanogaster.Biogerontology · 2021Article
- Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system.Scientific reports · 2021Article
- Mitochondrial alternative oxidase contributes to successful tardigrade anhydrobiosis.Frontiers in zoology · 2021Article
- The tardigrade Hypsibius exemplaris has the active mitochondrial alternative oxidase that could be studied at animal organismal level.PloS one · 2021Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyanide-resistant non-phosphorylating respiration is known in mitochondria from plants, fungi, and microorganisms but is absent in mammals. It results from the activity of an alternative oxidase (AOX) that conveys electrons directly from the respiratory chain (RC) ubiquinol pool to oxygen. AOX thus provides a bypath that releases constraints on the cytochrome pathway and prevents the over-reduction of the ubiquinone pool, a major source of superoxide. RC dysfunctions and deleterious superoxide overproduction are recurrent themes in human pathologies, ranging from neurodegenerative diseases to cancer, and may be instrumental in ageing. Thus, preventing RC blockade and excess superoxide production by means of AOX should be of considerable interest. However, because of its energy-dissipating properties, AOX might produce deleterious effects of its own in mammals. Here we show that AOX can be safely expressed in the mouse (MitAOX), with major physiological parameters being unaffected. It neither disrupted the activity of other RC components nor decreased oxidative phosphorylation in isolated mitochondria. It conferred cyanide-resistance to mitochondrial substrate oxidation and decreased reactive oxygen species (ROS) production upon RC blockade. Accordingly, AOX expression was able to support cyanide-resistant respiration by intact organs and to afford prolonged protection against a lethal concentration of gaseous cyanide in whole animals. Taken together, these results indicate that AOX expression in the mouse is innocuous and permits to overcome a RC blockade, while reducing associated oxidative insult. Therefore, the MitAOX mice represent a valuable tool in order to investigate the ability of AOX to counteract the panoply of mitochondrial-inherited diseases originating from oxidative phosphorylation defects.
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