ArticleNature structural & molecular biology2018
Mechanism of parkin activation by phosphorylation.
Article in Nature structural & molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 110 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.
- The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.Journal of translational medicine · 2025Pooled it
- Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2019Trial
- PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.EMBO reports · 2026Article
- Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026Review
- Mitophagy-mediated immune evasion: Shared strategies of pathogens.Redox biology · 2026Review
- Mechanisms and Therapeutic Potential of Targeting Mitophagy in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Evaluating Force Matching as a Parametrization Strategy for the CHARMM36m Force Field Using Phosphorylation.The journal of physical chemistry. B · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- Alternative Translation Initiation in PRKN Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target.Annals of neurology · 2026Article
- Mitochondrial homeostasis in bone aging: Unraveling dysfunctional pathways and developing precision therapies.Fundamental research · 2026Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Cis or trans: a puzzle of Parkin activation mechanism.Essays in biochemistry · 2026Review
- MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.Theranostics · 2026Review
- Modulation of mitochondrial quality control in sepsis by traditional Chinese medicine: mechanistic insights and translational perspectives.Frontiers in pharmacology · 2026Review
- Mitochondrial protein import stress in Parkinson's disease: the TOM/TIM-PINK1/Parkin-DELE1/HRI axis linking mitochondrial proteostasis to neuronal death.Frontiers in cell and developmental biology · 2026Review
- Novel insight into PINK1/parkin-associated autophagy implicated in Parkinson disease.Translational neuroscience · 2026Review
- Inferring residue level hydrogen deuterium exchange with ReX.Communications chemistry · 2025Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the ubiquitin ligase parkin are responsible for a familial form of Parkinson's disease. Parkin and the PINK1 kinase regulate a quality-control system for mitochondria. PINK1 phosphorylates ubiquitin on the outer membrane of damaged mitochondria, thus leading to recruitment and activation of parkin via phosphorylation of its ubiquitin-like (Ubl) domain. Here, we describe the mechanism of parkin activation by phosphorylation. The crystal structure of phosphorylated Bactrocera dorsalis (oriental fruit fly) parkin in complex with phosphorylated ubiquitin and an E2 ubiquitin-conjugating enzyme reveals that the key activating step is movement of the Ubl domain and release of the catalytic RING2 domain. Hydrogen/deuterium exchange and NMR experiments with the various intermediates in the activation pathway confirm and extend the interpretation of the crystal structure to mammalian parkin. Our results rationalize previously unexplained Parkinson's disease mutations and the presence of internal linkers that allow large domain movements in parkin.
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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.