ArticleThe EMBO journal2022
Structural basis for feedforward control in the PINK1/Parkin pathway.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- PINK1-Parkin pathway-mediated mitophagy in sepsis: friend or foe?Molecular biology reports · 2026Review
- Alternative Translation Initiation in PRKN Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target.Annals of neurology · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- Phospho-ubiquitin: rewriting the ubiquitin code.Molecular neurodegeneration · 2026Review
- Cis or trans: a puzzle of Parkin activation mechanism.Essays in biochemistry · 2026Review
- Mitochondrial homeostasis meets novel programmed cell death: crosstalk mechanisms underlying cardiovascular diseases progression.Cell communication and signaling : CCS · 2026Review
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.Theranostics · 2026Review
- Novel insight into PINK1/parkin-associated autophagy implicated in Parkinson disease.Translational neuroscience · 2026Review
- The absence of Parkin in hTau mice leads to synaptic mitochondrial dysfunction, alterations to the synaptic proteome, and increased phosphorylated tau in the Hippocampus.Neurobiology of disease · 2025Article
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Ubiquitin system mutations in neurological diseases.Trends in biochemical sciences · 2024Review
- Activation of parkin by a molecular glue.Nature communications · 2024Article
- Naturally occurring hyperactive variants of human parkin.Communications biology · 2024Article
- PRKN-linked familial Parkinson's disease: cellular and molecular mechanisms of disease-linked variants.Cellular and molecular life sciences : CMLS · 2024Review
- Potential application of traditional Chinese medicine in age-related macular degeneration-focusing on mitophagy.Frontiers in pharmacology · 2024Review
- A PINK1 input threshold arises from positive feedback in the PINK1/Parkin mitophagy decision circuit.Cell reports · 2023Article
- Feedforward activation of PRKN/parkin.Autophagy · 2023Article
- Mitophagy in atherosclerosis: from mechanism to therapy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
PINK1 and parkin constitute a mitochondrial quality control system mutated in Parkinson's disease. PINK1, a kinase, phosphorylates ubiquitin to recruit parkin, an E3 ubiquitin ligase, to mitochondria. PINK1 controls both parkin localization and activity through phosphorylation of both ubiquitin and the ubiquitin-like (Ubl) domain of parkin. Here, we observed that phospho-ubiquitin can bind to two distinct sites on parkin, a high-affinity site on RING1 that controls parkin localization and a low-affinity site on RING0 that releases parkin autoinhibition. Surprisingly, ubiquitin vinyl sulfone assays, ITC, and NMR titrations showed that the RING0 site has higher affinity for phospho-ubiquitin than phosphorylated Ubl in trans. We observed parkin activation by micromolar concentrations of tetra-phospho-ubiquitin chains that mimic mitochondria bearing multiple phosphorylated ubiquitins. A chimeric form of parkin with the Ubl domain replaced by ubiquitin was readily activated by PINK1 phosphorylation. In all cases, mutation of the binding site on RING0 abolished parkin activation. The feedforward mechanism of parkin activation confers robustness and rapidity to the PINK1-parkin pathway and likely represents an intermediate step in its evolutionary development.
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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.