FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis.

ABSTRACT: Lipid droplets (LDs) are organelles that store and supply lipids based on cellular needs. While mechanisms preventing oxidative damage to membrane phospholipids are established, the vulnerability of LD neutral lipids to peroxidation and protective mechanisms are unknown. Here, we identify LD-localized Ferroptosis Suppressor Protein 1 (FSP1) as a critical regulator that prevents neutral lipid peroxidation by recycling coenzyme Q10 (CoQ10) to its lipophilic antioxidant form. Lipidomics reveal that FSP1 loss leads to the accumulation of oxidized triacylglycerols and cholesteryl esters, and biochemical reconstitution of FSP1 with CoQ10 and NADH suppresses triacylglycerol peroxidation in vitro. Notably, polyunsaturated fatty acid (PUFA)-rich triacylglycerols enhance cancer cell sensitivi

SUBMITTER: Lange M 

PROVIDER: S-EPMC11741373 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature