ArticleRedox biology2021
A novel role of KEAP1/PGAM5 complex: ROS sensor for inducing mitophagy.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 83 citations in OpenAlex.
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- Targeted degradation of hepatic KEAP1 mitigates drug-induced liver injury via dual boosting NRF2 and PGAM5 signaling.Redox biology · 2026Article
- Redox-regulated cell death in gastric cancer: Molecular insights and therapeutic opportunities.Journal of physiology and biochemistry · 2026Review
- The mtROS-Mitophagy Axis: A Decisive Redox Hub Governing Cell Fate in Myocardial Ischemia-Reperfusion Injury.Cardiovascular toxicology · 2026Review
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- Redox rhythms promote fitness by modulating ageing-dependent reprogramming.Nature metabolism · 2026Article
- Amyloid precursor protein interacts with the mitochondrial phosphatase PGAM5 and regulates mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- Novel mechanism of neuronal hypoxia response: HIF-1α/STOML2 mediated PINK1-dependent mitophagy activation against neuronal injury.Cell death discovery · 2026Article
- CDK12 Inactivation Attenuates Prostate Cancer Progression by Inhibiting BNIP3-Mediated Mitophagy.Cell proliferation · 2026Article
- TM4SF5-mediated KEAP1 Regulation in Hepatocytes Irrelevant to NRF2 Expression and Activity Promotes Oxidative Stress and Inflammation to Develop Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of biological sciences · 2026Article
- Lycopene Alleviates Deoxynivalenol-Induced Porcine Intestinal Epithelial Barrier Injury by Inhibiting PGAM5-Mediated Mitophagy-Dependent Ferroptosis.Research (Washington, D.C.) · 2026Article
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- An Integrated Multi-Omics Analysis Identifies Oxeiptosis-Related Biomarkers in Diabetic Retinopathy.Biomedicines · 2025Article
- Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- PGAM5 cleavage and oligomerization equilibrates mitochondrial dynamics under stress by regulating DRP1 function.Journal of cell science · 2025Article
- A Trichinella spiralis serine protease triggers gut epithelial apoptosis and destroys the barrier integrity to mediate larval invasion.PLoS neglected tropical diseases · 2025Article
- Cu-Mn Bimetallic Mesoporous Silica Nanosonosensitizers Enable Oxeiptosis-Mediated Sonodynamic Therapy for Ultra-Minimally Invasive Treatment of Benign Prostatic Hyperplasia.ACS applied materials & interfaces · 2025Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When ROS production exceeds the cellular antioxidant capacity, the cell needs to eliminate the defective mitochondria responsible for excessive ROS production. It has been proposed that the removal of these defective mitochondria involves mitophagy, but the mechanism of this regulation remains unclear. Here, we demonstrate that moderate mitochondrial superoxide and hydrogen peroxide production oxidates KEAP1, thus breaking the interaction between this protein and PGAM5, leading to the inhibition of its proteasomal degradation. Accumulated PGAM5 interferes with the processing of the PINK1 in the mitochondria leading to the accumulation of PINK1 on the outer mitochondrial membrane. In turn, PINK1 promotes Parkin recruitment to mitochondria and sensitizes mitochondria for autophagic removal. We also demonstrate that inhibitors of the KEAP1-PGAM5 protein-protein interaction (including CPUY192018) mimic the effect of mitochondrial ROS and sensitize mitophagy machinery, suggesting that these inhibitors could be used as pharmacological regulators of mitophagy. Together, our results show that KEAP1/PGAM5 complex senses mitochondrially generated superoxide/hydrogen peroxide to induce mitophagy.
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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.