Glycerol 3-phosphate acyltransferase exacerbates α-synuclein-induced toxicity by increasing lipid peroxidation.

ABSTRACT: Although multiple cellular pathways have been implicated in α-Synuclein (α-syn)-associated Parkinson's disease (PD), the role of lipid metabolism remains elusive. In this study, we identify Drosophila mino, which encodes the mitochondrial isoform of the lipid synthesis enzyme glycerol 3-phosphate acyltransferase (GPAT), as a potent modifier of α-syn. Silencing the expression of mino significantly suppresses α-syn-induced PD phenotypes in Drosophila, including dopaminergic neuronal loss and locomotion defects as well as circadian rhythm-related activities, whereas mino overexpression yields opposite effects. Mechanistically, we find that mino modulates the levels of mitochondrial reactive oxygen species and lipid peroxidation. Importantly, treatment of α-syn-expressing flies with FSG67, a G

SUBMITTER: Ren M 

PROVIDER: S-EPMC12905208 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature