Condensate-Driven Triglyceride Depletion Links α-Synuclein to Mitochondrial Dysfunction.

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

SUBMITTER: Zhang T 

PROVIDER: S-EPMC12633352 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature