ArticleMolecular neurodegeneration2017
Quantitative proteomic analysis of Parkin substrates in Drosophila neurons.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- A guide to mapping ubiquitin and ubiquitin-like E3 ligases to their substrates.The FEBS journal · 2026Review
- Parkin Deficiency Impairs ER-Mitochondria Associations and calcium homeostasis via IP3R-Grp75-VDAC1 Complex.International journal of biological sciences · 2026Article
- The embedding of stress: mitophagy as a mechanism for the central nervous system (CNS) programming and lifelong disease vulnerability.Frontiers in cell and developmental biology · 2026Review
- Insights into PINK1/Parkin function and dysfunction from Drosophila models.The Biochemical journal · 2025Review
- Multifaceted role of nitric oxide in vascular dementia.Medical gas research · 2025Review
- Fbxo42 promotes the degradation of Ataxin-2 granules to trigger terminal Xbp1 signaling.Nature communications · 2025Article
- Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy.Nature communications · 2025Article
- Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.iScience · 2025Article
- SFXN2 contributes mitochondrial dysfunction-induced apoptosis as a substrate of Parkin.Frontiers in cellular neuroscience · 2025Article
- Mass spectrometry-based proteomics for biomarker discovery in theNeuroprotection (Chichester, England) · 2024Review
- Iron-sulfur cluster loss in mitochondrial CISD1 mediates PINK1 loss-of-function phenotypes.eLife · 2024Article
- In Silico Investigation of Parkin-Activating Mutations Using Simulations and Network Modeling.Biomolecules · 2024Article
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Parkin inhibits proliferation and migration of bladder cancer via ubiquitinating Catalase.Communications biology · 2024Article
- Mitochondrial CISD1/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes in Pink1/parkin models.Molecular neurodegeneration · 2024Article
- PINK1 and Parkin regulate IPNature communications · 2023Article
- P-Rex1 is a novel substrate of the E3 ubiquitin ligase Malin associated with Lafora disease.Neurobiology of disease · 2023Article
- Post-translational modification and mitochondrial function in Parkinson's disease.Frontiers in molecular neuroscience · 2023Review
- Receptor Recycling by Retromer.Molecular and cellular biology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundParkin (PARK2) is an E3 ubiquitin ligase that is commonly mutated in Familial Parkinson's Disease (PD). In cell culture models, Parkin is recruited to acutely depolarised mitochondria by PINK1. PINK1 activates Parkin activity leading to ubiquitination of multiple proteins, which in turn promotes clearance of mitochondria by mitophagy. Many substrates have been identified using cell culture models in combination with depolarising drugs or proteasome inhibitors, but not in more physiological settings.
methodsHere we utilized the recently introduced BioUb strategy to isolate ubiquitinated proteins in flies. Following Parkin Wild-Type (WT) and Parkin Ligase dead (LD) expression we analysed by mass spectrometry and stringent bioinformatics analysis those proteins differentially ubiquitinated to provide the first survey of steady state Parkin substrates using an in vivo model. We further used an in vivo ubiquitination assay to validate one of those substrates in SH-SY5Y cells.
resultsWe identified 35 proteins that are more prominently ubiquitinated following Parkin over-expression. These include several mitochondrial proteins and a number of endosomal trafficking regulators such as v-ATPase sub-units, Syx5/STX5, ALiX/PDCD6IP and Vps4. We also identified the retromer component, Vps35, another PD-associated gene that has recently been shown to interact genetically with parkin. Importantly, we validated Parkin-dependent ubiquitination of VPS35 in human neuroblastoma cells.
conclusionsCollectively our results provide new leads to the possible physiological functions of Parkin activity that are not overtly biased by acute mitochondrial depolarisation.
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