ArticleThe EMBO journal2015
A Ubl/ubiquitin switch in the activation of Parkin.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
What it found
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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
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 214 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
- Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism.Brain : a journal of neurology · 2017Pooled it
- Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026Review
- Regulation of cellular proteostasis via mitochondrial protein import.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.EMBO reports · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- Cis or trans: a puzzle of Parkin activation mechanism.Essays in biochemistry · 2026Review
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.Autophagy · 2025Article
- Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress.Science advances · 2025Article
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Stressful situations: Molecular insights on mitochondrial quality control pathways.The Journal of biological chemistry · 2025Review
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- Phosphorylation of Optineurin by protein kinase D regulates Parkin-dependent mitophagy.iScience · 2024Article
- Cooperative Substructure and Energetics of Allosteric Regulation of the Catalytic Core of the E3 Ubiquitin Ligase Parkin by Phosphorylated Ubiquitin.Biomolecules · 2024Article
- The role of PINK1-Parkin in mitochondrial quality control.Nature cell biology · 2024Review
- Activation of parkin by a molecular glue.Nature communications · 2024Article
- Additional feedforward mechanism of Parkin activation via binding of phospho-UBL and RING0 ineLife · 2024Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in Parkin and PINK1 cause an inherited early-onset form of Parkinson's disease. The two proteins function together in a mitochondrial quality control pathway whereby PINK1 accumulates on damaged mitochondria and activates Parkin to induce mitophagy. How PINK1 kinase activity releases the auto-inhibited ubiquitin ligase activity of Parkin remains unclear. Here, we identify a binding switch between phospho-ubiquitin (pUb) and the ubiquitin-like domain (Ubl) of Parkin as a key element. By mutagenesis and SAXS, we show that pUb binds to RING1 of Parkin at a site formed by His302 and Arg305. pUb binding promotes disengagement of the Ubl from RING1 and subsequent Parkin phosphorylation. A crystal structure of Parkin Δ86-130 at 2.54 Å resolution allowed the design of mutations that specifically release the Ubl domain from RING1. These mutations mimic pUb binding and promote Parkin phosphorylation. Measurements of the E2 ubiquitin-conjugating enzyme UbcH7 binding to Parkin and Parkin E3 ligase activity suggest that Parkin phosphorylation regulates E3 ligase activity downstream of pUb binding.
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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.