ArticleInternational journal of molecular sciences2016
Metformin Restores Parkin-Mediated Mitophagy, Suppressed by Cytosolic p53.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 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
65 citing papers in PubMed, 94 citations in OpenAlex.
- Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness.Journal of Korean medical science · 2017Trial
- Metformin Ameliorates Diabetes-Associated Cognitive Dysfunction via p53/Parkin-Mediated Mitophagy.Diabetes, obesity & metabolism · 2026Article
- Rab1A Promotes Hepatic Steatosis by Suppressing Mitophagy via the Raf-1/ERK1/2/PINK1 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial DNA: a molecular switch driving sterile neuroinflammation.Translational neurodegeneration · 2026Review
- Repurposed metformin-apigenin combination therapy for metabolic dysfunction-associated steatohepatitis: from integrative multi-omics discovery toFrontiers in pharmacology · 2026Article
- Review
- Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Induction of Autophagy as a Therapeutic Breakthrough for NAFLD: Current Evidence and Perspectives.Biology · 2025Review
- The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease and future strategies for targeted therapy.European journal of medical research · 2025Review
- Flutamide Promotes Early Hepatocarcinogenesis Through Mitophagy in High-Fat Diet-Fed Non-Obese Steatotic Rats.International journal of molecular sciences · 2025Article
- A Comprehensive Review of Metabolic Dysfunction-Associated Steatotic Liver Disease: Its Mechanistic Development Focusing on Methylglyoxal and Counterbalancing Treatment Strategies.International journal of molecular sciences · 2025Review
- Upstream targeting for the prevention of atrial fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)-rationale and study design.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2025Article
- Mitophagy Unveiled: Exploring the Nexus of Mitochondrial Health and Neuroendocrinopathy.Journal of molecular neuroscience : MN · 2024Review
- Inhibition of mitochondrial OMA1 ameliorates osteosarcoma tumorigenesis.Cell death & disease · 2024Article
- Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.International journal of molecular sciences · 2024Review
- [Research Progress in Stress-Induced Senescence of Renal Tubular Cells in Diabetic Nephropathy].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Article
- Metformin inhibits inflammatory response and endoplasmic reticulum stress to improve hypothalamic aging in obese mice.iScience · 2023Article
- Review
- Review
- Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is known to alleviate hepatosteatosis by inducing 5' adenosine monophosphate (AMP)-kinase-independent, sirtuin 1 (SIRT1)-mediated autophagy. Dysfunctional mitophagy in response to glucolipotoxicities might play an important role in hepatosteatosis. Here, we investigated the mechanism by which metformin induces mitophagy through restoration of the suppressed Parkin-mediated mitophagy. To this end, our ob/ob mice were divided into three groups: (1) ad libitum feeding of a standard chow diet; (2) intraperitoneal injections of metformin 300 mg/kg; and (3) 3 g/day caloric restriction (CR). HepG2 cells were treated with palmitate (PA) plus high glucose in the absence or presence of metformin. We detected enhanced mitophagy in ob/ob mice treated with metformin or CR, whereas mitochondrial spheroids were observed in mice fed ad libitum. Metabolically stressed ob/ob mice and PA-treated HepG2 cells showed an increase in expression of endoplasmic reticulum (ER) stress markers and cytosolic p53. Cytosolic p53 inhibited mitophagy by disturbing the mitochondrial translocation of Parkin, as demonstrated by immunoprecipitation. However, metformin decreased ER stress and p53 expression, resulting in induction of Parkin-mediated mitophagy. Furthermore, pifithrin-α, a specific inhibitor of p53, increased mitochondrial incorporation into autophagosomes. Taken together, these results indicate that metformin treatment facilitates Parkin-mediated mitophagy rather than mitochondrial spheroid formation by decreasing the inhibitory interaction with cytosolic p53 and increasing degradation of mitofusins.
Indexed as
Identifiers
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.