ArticleThe Journal of biological chemistry2014
Soluble, prefibrillar α-synuclein oligomers promote complex I-dependent, Ca2+-induced mitochondrial dysfunction.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.
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Who cites it
170 citing papers in PubMed, 277 citations in OpenAlex.
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Perspectives on ionizing radiation and Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Large-scale visualization of α-synuclein oligomers in Parkinson's disease brain tissue.Nature biomedical engineering · 2026Article
- Unravelling the novel insights between miR-7 and Parkinson's disease (PD).Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- The conundrum of alpha-synuclein antibody failures in Parkinson's disease: a narrative review of mechanisms and alternative metabolic hypotheses.Therapeutic advances in neurological disorders · 2026Review
- Plasma α-synuclein and QSM-derived susceptibility in Parkinson's disease: associations with clinical features.Frontiers in aging neuroscience · 2026Article
- Internalized SNCA/α-synuclein fibrils become truncated and resist degradation in neurons while glial cells rapidly degrade SNCA fibrils.Autophagy · 2026Article
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Oxidative Stress in DNA Damage and Neurodegenerative Diseases: Unveiling The Mechanisms and Therapeutic Opportunities.Cell biochemistry and biophysics · 2025Review
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Review
- The development and emerging trends in Parkinson's disease from the perspective of mitochondrial dysfunction: a bibliometric analysis using CiteSpace.Journal of neurology · 2025Review
- Global kinetic model of lipid-inducedProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Is the Voltage-Dependent Anion Channel a Major Player in Neurodegenerative Diseases?International journal of molecular sciences · 2025Review
- Formation of seeding-competent α-synuclein aggregates in parkin-deficient iPSC-derived human neurons.NPJ Parkinson's disease · 2025Article
- Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.Behavioral and brain functions : BBF · 2025Review
- From Obesity to Mitochondrial Dysfunction in Peripheral Tissues and in the Central Nervous System.Biomolecules · 2025Review
- Plant-Based Inhibitors of Protein Aggregation.Biomolecules · 2025Review
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- NPT100-18A rescues mitochondrial oxidative stress and neuronal degeneration in human iPSC-based Parkinson's model.BMC neuroscience · 2025Article
110 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
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Abstract
α-Synuclein (αSyn) aggregation and mitochondrial dysfunction both contribute to the pathogenesis of Parkinson disease (PD). Although recent studies have suggested that mitochondrial association of αSyn may disrupt mitochondrial function, it is unclear what aggregation state of αSyn is most damaging to mitochondria and what conditions promote or inhibit the effect of toxic αSyn species. Because the neuronal populations most vulnerable in PD are characterized by large cytosolic Ca(2+) oscillations that burden mitochondria, we examined mitochondrial Ca(2+) stress in an in vitro system comprising isolated mitochondria and purified recombinant human αSyn in various aggregation states. Using fluorimetry to simultaneously measure four mitochondrial parameters, we observed that soluble, prefibrillar αSyn oligomers, but not monomeric or fibrillar αSyn, decreased the retention time of exogenously added Ca(2+), promoted Ca(2+)-induced mitochondrial swelling and depolarization, and accelerated cytochrome c release. Inhibition of the permeability transition pore rescued these αSyn-induced changes in mitochondrial parameters. Interestingly, the mitotoxic effects of αSyn were specifically dependent upon both electron flow through complex I and mitochondrial uptake of exogenous Ca(2+). Our results suggest that soluble prefibrillar αSyn oligomers recapitulate several mitochondrial phenotypes previously observed in animal and cell models of PD: complex I dysfunction, altered membrane potential, disrupted Ca(2+) homeostasis, and enhanced cytochrome c release. These data reveal how the association of oligomeric αSyn with mitochondria can be detrimental to the function of cells with high Ca(2+)-handling requirements.
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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.