ArticleEMBO reports2021
MITOL promotes cell survival by degrading Parkin during mitophagy.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Mechanisms and Therapeutic Potential of Targeting Mitophagy in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Review
- Decidual protein induced by progesterone enhances HIF-1α stability to promote mitophagy and glycolysis.The FEBS journal · 2026Article
- Mitochondria-ER contacts function as an iron supply hub.Nature cell biology · 2026Article
- Inhibition of NCOA4-mediated ferritinophagy improves cardiac remodeling in diabetic cardiomyopathy via MITOL/parkin signaling.Molecular and cellular biochemistry · 2026Article
- Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast accumulation by inhibiting Parkin-dependent mitophagy.Nature communications · 2026Article
- DAPK1-Mediated Parkin Inactivation Enhances Neurotoxicity via MITOL-Dependent Degradation.Journal of cellular and molecular medicine · 2026Article
- Article
- Glucose concentration of neuronal media formulations influences PINK1-dependent mitophagy in human iNeurons.Autophagy reports · 2026Article
- Novel insight into PINK1/parkin-associated autophagy implicated in Parkinson disease.Translational neuroscience · 2026Review
- Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.Autophagy · 2025Article
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Endothelial major vault protein alleviates vascular remodeling via promoting Parkin-mediated mitophagy.Nature communications · 2025Article
- The role of senescence-related genes in major depressive disorder: insights from machine learning and single cell analysis.BMC psychiatry · 2025Article
- Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis.Developmental cell · 2025Article
- Self-Healing COCu-Tac Hydrogel Enhances iNSCs Transplantation for Spinal Cord Injury by Promoting Mitophagy via the FKBP52/AKT Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging.Aging medicine (Milton (N.S.W)) · 2024Article
- The Role of Ubiquitin-Proteasome System and Mitophagy in the Pathogenesis of Parkinson's Disease.Neuromolecular medicine · 2023Review
- MARCH5-dependent NLRP3 ubiquitination is required for mitochondrial NLRP3-NEK7 complex formation and NLRP3 inflammasome activation.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkin promotes cell survival by removing damaged mitochondria via mitophagy. However, although some studies have suggested that Parkin induces cell death, the regulatory mechanism underlying the dual role of Parkin remains unknown. Herein, we report that mitochondrial ubiquitin ligase (MITOL/MARCH5) regulates Parkin-mediated cell death through the FKBP38-dependent dynamic translocation from the mitochondria to the ER during mitophagy. Mechanistically, MITOL mediates ubiquitination of Parkin at lysine 220 residue, which promotes its proteasomal degradation, and thereby fine-tunes mitophagy by controlling the quantity of Parkin. Deletion of MITOL leads to accumulation of the phosphorylated active form of Parkin in the ER, resulting in FKBP38 degradation and enhanced cell death. Thus, we have shown that MITOL blocks Parkin-induced cell death, at least partially, by protecting FKBP38 from Parkin. Our findings unveil the regulation of the dual function of Parkin and provide a novel perspective on the pathogenesis of PD.
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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.