ArticlePloS one2010
Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 1 of them a synthesis that pooled it.
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Who cites it
183 citing papers in PubMed, 1 synthesis or guideline pooled it, 377 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Hydrogen sulfide alleviates hyperoxia effects on mitochondria in human developing airway smooth muscle.JCI insight · 2026Article
- Mitochondrial Fission and Fusion Disorders and Autophagy Abnormalities in Parkinson's Disease.Neurochemical research · 2026Review
- Targeting oxidative stress and mitochondrial dysfunction via URG7 overexpression in an in vitro Parkinson's disease neuronal model.Scientific reports · 2026Article
- VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1-linked Parkinson's neurons.Science advances · 2026Article
- Ultrastructural perspectives on the enteric nervous system in Parkinson's disease.Frontiers in neuroscience · 2026Review
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria.Nature communications · 2025Article
- Parkinson Disease Signaling Pathways, Molecular Mechanisms, and Potential Therapeutic Strategies: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Application of IVDr NMR spectroscopy to stratify Parkinson's disease with absolute quantitation of blood serum metabolites and lipoproteins.Scientific reports · 2025Article
- Chaperone-mediated autophagy manipulates PGC1α stability and governs energy metabolism under thermal stress.Nature communications · 2025Article
- Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease.International journal of molecular sciences · 2025Review
- Redox modulatory role of DJ-1 in Parkinson's disease.Biogerontology · 2025Review
- Long-term exposure to PMScientific reports · 2025Article
- Effects of glial-derived neurotrophic factor on remodeling and mitochondrial function in human airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- PARK7/DJ-1 deficiency impairs microglial activation in response to LPS-induced inflammation.Journal of neuroinflammation · 2024Article
- Key genes and convergent pathogenic mechanisms in Parkinson disease.Nature reviews. Neuroscience · 2024Review
- Ablation of Mitochondrial RCC1-L Induces Nigral Dopaminergic Neurodegeneration and Parkinsonian-like Motor Symptoms.bioRxiv : the preprint server for biology · 2024Article
- Review
- Mitochondrial Dysfunction and Protein Homeostasis in Aging: Insights from a Premature-Aging Mouse Model.Biomolecules · 2024Article
123 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitochondrial dysfunction and degradation takes a central role in current paradigms of neurodegeneration in Parkinson's disease (PD). Loss of DJ-1 function is a rare cause of familial PD. Although a critical role of DJ-1 in oxidative stress response and mitochondrial function has been recognized, the effects on mitochondrial dynamics and downstream consequences remain to be determined. METHODOLOGY/PRINCIPAL
findingsUsing DJ-1 loss of function cellular models from knockout (KO) mice and human carriers of the E64D mutation in the DJ-1 gene we define a novel role of DJ-1 in the integrity of both cellular organelles, mitochondria and lysosomes. We show that loss of DJ-1 caused impaired mitochondrial respiration, increased intramitochondrial reactive oxygen species, reduced mitochondrial membrane potential and characteristic alterations of mitochondrial shape as shown by quantitative morphology. Importantly, ultrastructural imaging and subsequent detailed lysosomal activity analyses revealed reduced basal autophagic degradation and the accumulation of defective mitochondria in DJ-1 KO cells, that was linked with decreased levels of phospho-activated ERK2. CONCLUSIONS/SIGNIFICANCE: We show that loss of DJ-1 leads to impaired autophagy and accumulation of dysfunctional mitochondria that under physiological conditions would be compensated via lysosomal clearance. Our study provides evidence for a critical role of DJ-1 in mitochondrial homeostasis by connecting basal autophagy and mitochondrial integrity in Parkinson's disease.
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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.