ArticleNature neuroscience2022
Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity.
Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 135 papers, 1 of them a synthesis that pooled it.
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Who cites it
135 citing papers in PubMed, 1 synthesis or guideline pooled it, 230 citations in OpenAlex.
- Hepatitis C virus infection and Parkinson's disease: insights from a joint sex-stratified BioOptimatics meta-analysis.Scientific reports · 2024Pooled it
- High-resolution NMR spectroscopy of proteins in intact mitochondria.Nature chemical biology · 2026Article
- Sex-specific regulation of angiogenin in Alzheimer's disease.Molecular psychiatry · 2026Article
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Review
- Regional reduction of high-energy phosphorus metabolites characterizes the cerebellar subtype of multiple system atrophy.NPJ Parkinson's disease · 2026Article
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation.FEBS open bio · 2026Article
- Lipid droplets promote aberrant liquid-liquid phase separation of alpha-synuclein impairing energy homeostasis.EMBO reports · 2026Article
- Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- ADT-OH promotes mitophagy and suppresses the cytosolic mtDNA-cGAS-STING inflammatory cascade in microglia.Acta pharmacologica Sinica · 2026Article
- Tracking Gene Expression of Single Mitochondria in Live Neurons Using Nanotweezers.Journal of the American Chemical Society · 2026Article
- HM568 Enhances NADMolecular neurobiology · 2026Article
- Upregulated PKM2 Protects Dopaminergic Neurons From Oxidative Damage Through Nrf2 Transactivation in an MPTP-Induced Mouse Model of Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- Large-scale visualization of α-synuclein oligomers in Parkinson's disease brain tissue.Nature biomedical engineering · 2026Article
- Pathogenic variants in the autophagy-tethering factor EPG5 drive neurodegeneration through mitochondrial dysfunction and innate immune activation.Nature communications · 2026Article
- α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron-microglia communication.Nature communications · 2026Article
- Triose phosphate isomerase 1 remodels mitochondrial cristae ultrastructure to rewire microglial immunometabolism against ischemic stroke.Nature communications · 2026Article
- Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.Molecular neurobiology · 2026Review
- Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling.bioRxiv : the preprint server for biology · 2026Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
30 authors at 9 institutions in 4 countries.
Funding
Abstract
Aggregation of alpha-synuclein (α-Syn) drives Parkinson's disease (PD), although the initial stages of self-assembly and structural conversion have not been directly observed inside neurons. In this study, we tracked the intracellular conformational states of α-Syn using a single-molecule Förster resonance energy transfer (smFRET) biosensor, and we show here that α-Syn converts from a monomeric state into two distinct oligomeric states in neurons in a concentration-dependent and sequence-specific manner. Three-dimensional FRET-correlative light and electron microscopy (FRET-CLEM) revealed that intracellular seeding events occur preferentially on membrane surfaces, especially at mitochondrial membranes. The mitochondrial lipid cardiolipin triggers rapid oligomerization of A53T α-Syn, and cardiolipin is sequestered within aggregating lipid-protein complexes. Mitochondrial aggregates impair complex I activity and increase mitochondrial reactive oxygen species (ROS) generation, which accelerates the oligomerization of A53T α-Syn and causes permeabilization of mitochondrial membranes and cell death. These processes were also observed in induced pluripotent stem cell (iPSC)-derived neurons harboring A53T mutations from patients with PD. Our study highlights a mechanism of de novo α-Syn oligomerization at mitochondrial membranes and subsequent neuronal toxicity.
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Registered trials
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.