ArticleOpen biology2022
Selective localization of Mfn2 near PINK1 enables its preferential ubiquitination by Parkin on mitochondria.
Article in Open biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Unraveling Parkinson's disease: The mystery of mitochondria and the role of aging.Genes & diseases · 2026Review
- Mitochondrial homeostasis meets novel programmed cell death: crosstalk mechanisms underlying cardiovascular diseases progression.Cell communication and signaling : CCS · 2026Review
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- A review of the protection mechanisms of ginsenoside CK on cardiovascular disease and stroke.Frontiers in pharmacology · 2026Review
- A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1.The Journal of cell biology · 2025Article
- The role of cardiolipin in mitochondrial dynamics and quality control in neuronal ischemia/reperfusion injury.Cell death & disease · 2025Review
- Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH.Translational stroke research · 2025Article
- Mitochondria at the Crossroads: Linking the Mediterranean Diet to Metabolic Health and Non-Pharmacological Approaches to NAFLD.Nutrients · 2025Review
- The multifaceted role of mitochondria in cardiac function: insights and approaches.Cell communication and signaling : CCS · 2024Review
- The role of PINK1-Parkin in mitochondrial quality control.Nature cell biology · 2024Review
- Naturally occurring hyperactive variants of human parkin.Communications biology · 2024Article
- Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy.Journal of translational medicine · 2023Review
- Structure-based design and characterization of Parkin-activating mutations.Life science alliance · 2023Article
- NAFLD: Mechanisms, Treatments, and Biomarkers.Biomolecules · 2022Review
- Nuclear and Cytoplasmatic Players in Mitochondria-Related CNS Disorders: Chromatin Modifications and Subcellular Trafficking.Biomolecules · 2022Review
- Mechanisms underlying ubiquitin-driven selective mitochondrial and bacterial autophagy.Molecular cell · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in Parkin and PINK1 cause early-onset familial Parkinson's disease. Parkin is a RING-In-Between-RING E3 ligase that transfers ubiquitin from an E2 enzyme to a substrate in two steps: (i) thioester intermediate formation on Parkin and (ii) acyl transfer to a substrate lysine. The process is triggered by PINK1, which phosphorylates ubiquitin on damaged mitochondria, which in turn recruits and activates Parkin. This leads to the ubiquitination of outer mitochondrial membrane proteins and clearance of the organelle. While the targets of Parkin on mitochondria are known, the factors determining substrate selectivity remain unclear. To investigate this, we examined how Parkin catalyses ubiquitin transfer to substrates. We found that His433 in the RING2 domain contributes to the catalysis of acyl transfer. In cells, the mutation of His433 impairs mitophagy. In vitro ubiquitination assays with isolated mitochondria show that Mfn2 is a kinetically preferred substrate. Using proximity-ligation assays, we show that Mfn2 specifically co-localizes with PINK1 and phospho-ubiquitin (pUb) in U2OS cells upon mitochondrial depolarization. We propose a model whereby ubiquitination of Mfn2 is efficient by virtue of its localization near PINK1, which leads to the recruitment and activation of Parkin via pUb at these sites.
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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.