Lipid droplets promote aberrant liquid-liquid phase separation of alpha-synuclein impairing energy homeostasis

ABSTRACT: Alpha-synuclein (αSyn) inclusions are a defining neuropathological feature of Parkinson's disease, but the cellular events that initiate their formation and promote neurotoxicity remain incompletely understood. Aberrant liquid-liquid phase separation has emerged as a potential early step in αSyn dysregulation, yet the physiological triggers and functional consequences of this process are unclear. Here, we show that lipid droplets promote the spontaneous phase separation of wild-type and E46K mutant αSyn into condensates. These condensates sequester lipid droplets and impair their turnover, indicating disruption of cellular lipid homeostasis. Mitochondria in close proximity to αSyn condensates exhibit reduced membrane potential and increased mitophagy. Correlative light and electron microsc

SUBMITTER: Jose Cevallos 

PROVIDER: S-SCDT-10_1038-S44319-026-00856-8 | biostudies-other |

REPOSITORIES: biostudies-other