ArticlePLoS genetics2014
Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 192 citations in OpenAlex.
- Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism.Brain : a journal of neurology · 2017Pooled it
- USP18 exacerbates myocardial I/R injury by inhibiting Parkin mitophagy through the deubiquitinase PTEN-L.Military Medical Research · 2026Article
- Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- In vitro and in vivo rescue of dopaminergic neurons in Parkinson's disease models after Parkin gene therapy.Gene therapy · 2026Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- The C-Terminal Regions of TRAK Proteins Contain MIRO-Independent Mitochondrial Localization Domains.Cytoskeleton (Hoboken, N.J.) · 2026Article
- Cis or trans: a puzzle of Parkin activation mechanism.Essays in biochemistry · 2026Review
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Article
- PINK1 Loss of Function Selectively Alters the Mitochondrial-Derived Vesicle Pathway.FASEB bioAdvances · 2025Article
- A positive feedback loop between SMAD3 and PINK1 in regulation of mitophagy.Cell discovery · 2025Article
- Rnf40 Exacerbates Hypertension-Induced Cerebrovascular Endothelial Barrier Dysfunction by Ubiquitination and Degradation of Parkin.CNS neuroscience & therapeutics · 2025Article
- Role of AMBRA1 in mitophagy regulation: emerging evidence in aging-related diseases.Autophagy · 2024Review
- Additional feedforward mechanism of Parkin activation via binding of phospho-UBL and RING0 ineLife · 2024Article
- Capturing the catalytic intermediates of parkin ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pathogenesis of Parkinson's disease: from hints from monogenic familial PD to biomarkers.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- KAT8 compound inhibition inhibits the initial steps of PINK1-dependant mitophagy.Scientific reports · 2024Article
- Tom20 gates PINK1 activity and mediates its tethering of the TOM and TIM23 translocases upon mitochondrial stress.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Alterations of PINK1-PRKN signaling in mice during normal aging.Autophagy reports · 2024Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kinase PINK1 and the E3 ubiquitin (Ub) ligase Parkin participate in mitochondrial quality control. The phosphorylation of Ser65 in Parkin's ubiquitin-like (UBl) domain by PINK1 stimulates Parkin activation and translocation to damaged mitochondria, which induces mitophagy generating polyUb chain. However, Parkin Ser65 phosphorylation is insufficient for Parkin mitochondrial translocation. Here we report that Ser65 in polyUb chain is also phosphorylated by PINK1, and that phosphorylated polyUb chain on mitochondria tethers Parkin at mitochondria. The expression of Tom70MTS-4xUb SE, which mimics phospho-Ser65 polyUb chains on the mitochondria, activated Parkin E3 activity and its mitochondrial translocation. An E3-dead form of Parkin translocated to mitochondria with reduced membrane potential in the presence of Tom70(MTS)-4xUb SE, whereas non-phospho-polyUb mutant Tom70(MTS)-4xUb SA abrogated Parkin translocation. Parkin binds to the phospho-polyUb chain through its RING1-In-Between-RING (IBR) domains, but its RING0-linker is also required for mitochondrial translocation. Moreover, the expression of Tom70(MTS)-4xUb SE improved mitochondrial degeneration in PINK1-deficient, but not Parkin-deficient, Drosophila. Our study suggests that the phosphorylation of mitochondrial polyUb by PINK1 is implicated in both Parkin activation and mitochondrial translocation, predicting a chain reaction mechanism of mitochondrial phospho-polyUb production by which rapid translocation of Parkin is achieved.
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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.