ArticleTranslational neurodegeneration2021
Parkinson's disease-associated VPS35 mutant reduces mitochondrial membrane potential and impairs PINK1/Parkin-mediated mitophagy.
Article in Translational neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Decode the Ubiquitinome in Parkinson's Disease: From Pathological Aggregates to Targeted DUB Therapeutics.Neuroscience bulletin · 2026Review
- VPS35 mutation inhibits PINK1/parkin-mediated mitophagy via increased LRRK2 kinase activity.Brain : a journal of neurology · 2026Article
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- Senescent BMSC-Derived Thbs1 Drives Inflammaging and Impairs Bone Regeneration by Suppressing PINK1/Parkin-Mediated Mitophagy in Macrophages.Aging cell · 2026Article
- AWmeta Empowers Adaptively Weighted Transcriptomic Meta-Analysis.Current issues in molecular biology · 2026Article
- Extracellular vesicles from IPFP-MSCs trigger osteoarthritis by transferring mtDNA.Bioactive materials · 2026Article
- Dietary chromium picolinate-promoted oxidative phosphorylation may be a potential mean to improve hypoxia tolerance of juvenile grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Context-dependent ATP7 Interactions with Parkinson's Disease-associated Genes Modulate Copper Homeostasis Phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Novel insight into PINK1/parkin-associated autophagy implicated in Parkinson disease.Translational neuroscience · 2026Review
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- Isoniazid potentiates tigecycline to kill methicillin-resistantEmerging microbes & infections · 2025Article
- Review
- Mapping the global research landscape of mitophagy in Parkinson's disease: a bibliometric and visualization analysis.Hereditas · 2025Article
- Targeting Mitochondrial Quality Control for the Treatment of Triple-Negative Breast Cancer: From Molecular Mechanisms to Precision Therapy.Biomolecules · 2025Review
- LRRK2-mediated mitochondrial dysfunction in Parkinson's disease.The Biochemical journal · 2025Review
- Degenerative Disease Diagnosis and Analysis Based on Tissue Specificity of DNA Methylation.International journal of molecular sciences · 2025Article
- Exercise regulates mitophagy to alleviate parkinsonian neurodegeneration.Frontiers in aging neuroscience · 2025Review
- VPS35-Retromer: Multifunctional Roles in Various Biological Processes - A Focus on Neurodegenerative Diseases and Cancer.Journal of inflammation research · 2025Review
- Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes.Nature communications · 2024Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMitochondrial dysfunction plays a prominent role in the pathogenesis of Parkinson's disease (PD), and several genes linked to familial PD, including PINK1 (encoding PTEN-induced putative kinase 1 [PINK1]) and PARK2 (encoding the E3 ubiquitin ligase Parkin), are directly involved in processes such as mitophagy that maintain mitochondrial health. The dominant p.D620N variant of vacuolar protein sorting 35 ortholog (VPS35) gene is also associated with familial PD but has not been functionally connected to PINK1 and PARK2.
methodsTo better mimic and study the patient situation, we used CRISPR-Cas9 to generate heterozygous human SH-SY5Y cells carrying the PD-associated D620N variant of VPS35. These cells were treated with a protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) to induce the PINK1/Parkin-mediated mitophagy, which was assessed using biochemical and microscopy approaches.
resultsMitochondria in the VPS35-D620N cells exhibited reduced mitochondrial membrane potential and appeared to already be damaged at steady state. As a result, the mitochondria of these cells were desensitized to the CCCP-induced collapse in mitochondrial potential, as they displayed altered fragmentation and were unable to accumulate PINK1 at their surface upon this insult. Consequently, Parkin recruitment to the cell surface was inhibited and initiation of the PINK1/Parkin-dependent mitophagy was impaired.
conclusionOur findings extend the pool of evidence that the p.D620N mutation of VPS35 causes mitochondrial dysfunction and suggest a converging pathogenic mechanism among VPS35, PINK1 and Parkin in PD.
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