ArticleNature medicine2016
Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 2 of them syntheses that pooled it.
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Who cites it
204 citing papers in PubMed, 2 syntheses or guidelines pooled it, 322 citations in OpenAlex.
- Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease.Frontiers in aging neuroscience · 2022Pooled it
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Parkinson's disease-linked D620N mutation selectively alters the brain-specific protein interactome of VPS35.Neurobiology of disease · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- A Quarter Century of EHD Protein Research: From Endosomal Recycling to Ciliopathies.Traffic (Copenhagen, Denmark) · 2026Review
- The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.Molecular and cellular biochemistry · 2026Review
- Neuroimmune Regulation of NLRP3 Signalling in Parkinson's Disease.Molecular neurobiology · 2026Review
- VPS35 mutation inhibits PINK1/parkin-mediated mitophagy via increased LRRK2 kinase activity.Brain : a journal of neurology · 2026Article
- The Legionella effector RidL binds the large fission GTPase Drp1 to promote mitochondrial fragmentation.EMBO reports · 2026Article
- Article
- The vicious cycle: unraveling the interplay between α-synuclein, mitochondrial dysfunction, and neuroinflammation in Parkinson's disease.Journal of neurology · 2026Review
- Mitochondria-derived vesicles with bioenergetic units from brown adipose tissue attenuate cardiac remodeling post-myocardial infarction.Nature communications · 2026Article
- Salidroside Protects Against Simazine-Induced Neurotoxicity by ActivatingInternational journal of molecular sciences · 2026Article
- Parkinson's disease-linked D620N mutation selectively alters the brain-specific protein interactome of VPS35.bioRxiv : the preprint server for biology · 2026Article
- DAPK1-Mediated Parkin Inactivation Enhances Neurotoxicity via MITOL-Dependent Degradation.Journal of cellular and molecular medicine · 2026Article
- Reversibility and therapeutic feasibility of DNM1L-associated neurodevelopmental disorders.Experimental & molecular medicine · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- MAPL regulates gasdermin-mediated release of mtDNA from lysosomes to drive pyroptotic cell death.Nature cell biology · 2025Article
- Metformin as a potential neuroprotective agent that influence Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
144 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 4 countries.
Funding
Abstract
Mitochondrial dysfunction represents a critical step during the pathogenesis of Parkinson's disease (PD), and increasing evidence suggests abnormal mitochondrial dynamics and quality control as important underlying mechanisms. The VPS35 gene, which encodes a key component of the membrane protein-recycling retromer complex, is the third autosomal-dominant gene associated with PD. However, how VPS35 mutations lead to neurodegeneration remains unclear. Here we demonstrate that PD-associated VPS35 mutations caused mitochondrial fragmentation and cell death in cultured neurons in vitro, in mouse substantia nigra neurons in vivo and in human fibroblasts from an individual with PD who has the VPS35(D620N) mutation. VPS35-induced mitochondrial deficits and neuronal dysfunction could be prevented by inhibition of mitochondrial fission. VPS35 mutants showed increased interaction with dynamin-like protein (DLP) 1, which enhanced turnover of the mitochondrial DLP1 complexes via the mitochondria-derived vesicle-dependent trafficking of the complexes to lysosomes for degradation. Notably, oxidative stress increased the VPS35-DLP1 interaction, which we also found to be increased in the brains of sporadic PD cases. These results revealed a novel cellular mechanism for the involvement of VPS35 in mitochondrial fission, dysregulation of which is probably involved in the pathogenesis of familial, and possibly sporadic, PD.
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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.