ArticleGeroScience2024
Mitochondrial complex I inhibition triggers NAD
Article in GeroScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Article
- PSG6: A mitochondrially-targeted gentisic acid derivative exerts antiplatelet action via mitochondrial complex I inhibition.Redox biology · 2026Article
- LDL oxidation and cerebrovascular aging: mechanisms of endothelial dysfunction, inflammation, and vascular cognitive impairment and dementia.Redox biology · 2026Review
- Energy Metabolism Under Stress: Late-Stage Leigh Syndrome Reveals Profound Cardiometabolic Perturbations in Ndufs4 KO Mice.Journal of inherited metabolic disease · 2026Article
- Ocular Toxicity and Mechanistic Investigation for Berberine and Its Metabolite Berberrubine on Zebrafish.Molecules (Basel, Switzerland) · 2025Article
- An Alternative Metabolic Pathway of Glucose Oxidation Induced by Mitochondrial Complex I Inhibition: Serinogenesis and Folate Cycling.International journal of molecular sciences · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Maternal Vitamin and Mineral Supplementation Affected Neonatal Gene Expression and Rewired Key Regulatory Genes Underlying Hepatic Metabolism.Animals : an open access journal from MDPI · 2025Article
- Molecular mechanisms of UCP1-independent thermogenesis: the role of futile cycles in energy dissipation.Journal of physiology and biochemistry · 2025Review
- Assembly and Comparative Analysis of Complete Mitochondrial Genome Sequence of Endangered Medicinal PlantCurrent issues in molecular biology · 2025Article
- Tissue-Specific Regulation of Fatty Acid Metabolism in a Mouse Model of Isolated Complex I Deficiency.Proteomics · 2025Article
- Rab11a-dependent recycling of Glut3 inhibits seizure-induced neuronal disulfidptosis by alleviating glucose deficiency.Cell & bioscience · 2025Article
- From Childhood Obesity to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Hyperlipidemia Through Oxidative Stress During Childhood.Metabolites · 2025Review
- Antifungal effects of Metformin against Candida albicans by autophagy regulation.Journal of microbiology (Seoul, Korea) · 2025Article
- Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.Frontiers in cell and developmental biology · 2025Article
- Anti-diabetic effects of Dachaihu decoction combined withFrontiers in cell and developmental biology · 2025Article
- Article
- HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of mitochondrial complex I (NADH dehydrogenase) is the primary mechanism of the antidiabetic drug metformin and various unrelated natural toxins. Complex I inhibition can also be induced by antidiabetic PPAR agonists, and it is elicited by methionine restriction, a nutritional intervention causing resistance to diabetes and obesity. Still, a comprehensible explanation to why complex I inhibition exerts antidiabetic properties and engenders metabolic inefficiency is missing. To evaluate this issue, we have systematically reanalyzed published transcriptomic datasets from MPP-treated neurons, metformin-treated hepatocytes, and methionine-restricted rats. We found that pathways leading to NADPH formation were widely induced, together with anabolic fatty acid biosynthesis, the latter appearing highly paradoxical in a state of mitochondrial impairment. However, concomitant induction of catabolic fatty acid oxidation indicated that complex I inhibition created a "futile" cycle of fatty acid synthesis and degradation, which was anatomically distributed between adipose tissue and liver in vivo. Cofactor balance analysis unveiled that such cycling would indeed be energetically futile (-3 ATP per acetyl-CoA), though it would not be redox-futile, as it would convert NADPH into respirable FADH
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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.