ArticleThe Biochemical journal2014
Metformin and respiratory chain complex I: the last piece of the puzzle?
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- Combined Administration of Metformin and Vitamin D: A Futuristic Approach for Management of Hyperglycemia.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Redox state and altered pyruvate metabolism contribute to a dose-dependent metformin-induced lactate production of human myotubes.American journal of physiology. Cell physiology · 2023Article
- Targeting Mitochondria with ClpP Agonists as a Novel Therapeutic Opportunity in Breast Cancer.Cancers · 2023Review
- Effect of metformin on intact mitochondria from liver and brain: Concept revisited.European journal of pharmacology · 2022Article
- Therapeutic vs. Suprapharmacological Metformin Concentrations: Different Effects on Energy Metabolism and Mitochondrial Function in Skeletal Muscle CellsFrontiers in pharmacology · 2022Article
- Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants.Nutrients · 2021Review
- Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?Frontiers in physiology · 2021Review
- Mitochondrial Complex I Inhibition by Metformin Limits Reperfusion Injury.The Journal of pharmacology and experimental therapeutics · 2019Article
- Metformin Results in Diametrically Opposed Effects by Targeting Non-Stem Cancer Cells but Protecting Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2019Article
- Role of Mitochondria in the Mechanism(s) of Action of Metformin.Frontiers in endocrinology · 2019Review
- mTOR Inhibitor Therapy and Metabolic Consequences: Where Do We Stand?Oxidative medicine and cellular longevity · 2018Review
- Article
- Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I.Cell death & disease · 2017Article
- Metformin: A Hopeful Promise in Aging Research.Cold Spring Harbor perspectives in medicine · 2016Review
- Energy disruptors: rising stars in anticancer therapy?Oncogenesis · 2016Review
- Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity.Aging and disease · 2016Review
- Selective inhibition of deactivated mitochondrial complex I by biguanides.Biochemistry · 2015Article
- Roles of Pyruvate, NADH, and Mitochondrial Complex I in Redox Balance and Imbalance in β Cell Function and Dysfunction.Journal of diabetes research · 2015Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is the most widely prescribed drug used to treat patients affected by Type 2 diabetes. Metformin has also been shown to prevent some forms of cell death; however, evidence suggests that it may have anti-neoplastic properties. All of these effects have been attributed to complex I inhibition, but the mechanism by which metformin leads to complex I inhibition is not fully understood. Although it has been reported that the incubation of functionally isolated complex I in the presence of high concentrations of metformin led to its inhibition, much lower concentrations of metformin have been shown to inhibit complex I in intact cells. In a recent issue of the Biochemical Journal, Bridges, Jones, Pollak and Hirst [(2014) Biochem. J. 462, 475-487] studied for the first time the effect of metformin on purified complex I. They report that millimolar concentrations of metformin directly inhibit complex I activity in a non-competitive manner. They also specify that the binding of metformin to complex I depends on its conformation. To explain the difference in concentration required to inhibit complex I in intact cells and on isolated enzyme, Bridges et al. (2014) propose that metformin concentrates within mitochondria in intact cells. Albeit theoretically plausible, this attractive hypothesis is not directly tested by Bridges et al. (2014) Moreover, although sparse, the current literature does not support this hypothesis.
Indexed as
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What Socratic 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 Socratic graph.