ArticleRedox biology2018
Metformin selectively targets redox control of complex I energy transduction.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 147 citations in OpenAlex.
- Changes in peripheral mitochondrial DNA copy number in metformin-treated women with polycystic ovary syndrome: a longitudinal study.Reproductive biology and endocrinology : RB&E · 2020Trial
- Divergent Retrograde Signaling Pathways Coordinate Longevity and Metformin Responses in Complex I and Complex IV DeficientbioRxiv : the preprint server for biology · 2026Article
- Oxidative Stress as a Pathophysiological Core of Obesity: Preclinical Evidence for Antioxidant-Based Therapy Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Metformin Attenuates Sepsis-Induced Cardiomyopathy via Inhibition of Reverse Electron Transfer at Mitochondrial Complex I.Biology · 2026Article
- Metformin in Diabetes and Beyond: Therapeutic Mechanisms, Lactic Acidosis, Organ-Specific Effects, and Nanotechnology-Based Delivery Strategies.Current medical science · 2026Review
- Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy.FEBS open bio · 2026Article
- Metformin treatment impairs the adenine nucleotide translocator activity and energy metabolism in human clear cell renal carcinoma cells.Scientific reports · 2026Article
- Complex I Modulator BI4500 Reduces MASH by Limiting Oxidative Stress and Reprogramming Lipid Metabolism via AMPK in MCD Rats.Antioxidants (Basel, Switzerland) · 2026Article
- Redox Homeostasis in Metabolic Syndrome and Type II Diabetes: Role of Skeletal Muscle and Impact of Gold-Standard Treatments.International journal of molecular sciences · 2025Review
- Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.Frontiers in cell and developmental biology · 2025Article
- Metformin may alter the course of Leber's hereditary optic neuropathy: a case report.Frontiers in medicine · 2025Article
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Metformin Impairs Linsitinib Anti-Tumor Effect on Ovarian Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Review
- Mitochondrial complex I inhibition triggers NADGeroScience · 2024Article
- Energy Metabolism and Metformin: Effects on Ischemia-Reperfusion Injury in Kidney Transplantation.Biomedicines · 2024Review
- The mitochondria as a potential therapeutic target in cerebral I/R injury.Frontiers in neuroscience · 2024Review
- Article
- Modulation of Mitochondrial Function as a Therapeutic Strategy for Neurodegenerative Diseases.The journal of prevention of Alzheimer's disease · 2023Review
- AMPK deficiency in smooth muscles causes persistent pulmonary hypertension of the new-born and premature death.Nature communications · 2022Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD
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What OpenQuestion holds
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.