Condensate-Driven Triglyceride Reduction Links α-Synuclein to Mitochondrial Dysfunction

ABSTRACT: α-Synuclein (αSyn) inclusions characterize multiple age-related neurodegenerative diseases, including Parkinson's disease (PD). While interactions between αSyn and lipids are known to contribute to αSyn pathobiology, the precise cellular mechanisms linking lipids to αSyn toxicity have yet to be elucidated. Through lipidomic profiling of Caenorhabditis elegans, we find that αSyn progressively alters lipid metabolism in aging worms. αSyn reduces the overall content of triacylglycerols (TAG) and disrupts the structure of lipid droplets (LD) and mitochondria. These pathological changes depend on αSyn's properties to bind lipid and to condensate into inclusions. Apart from lowering TAG levels, αSyn proportionally increases long-chain unsaturated fatty acids (LCUFAs). Consequently, genetic inhib

SUBMITTER: Tao Zhang 

PROVIDER: S-SCDT-10_1038-S44319-026-00954-7 | biostudies-other |

REPOSITORIES: biostudies-other