Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity - PubMed
3 hours ago
- #DGAT
- #lipid droplets
- #ferroptosis
- Lipid droplets (LDs) play dynamic roles in fatty acid metabolism, signaling, and trafficking.
- LDs can either mitigate or exacerbate lipotoxic damage by storing polyunsaturated fatty acids (PUFAs).
- Inhibition of DGAT-mediated LD biogenesis in triple-negative breast cancer cells promotes lipid peroxidation and ferroptosis sensitivity.
- LDs sequester PUFAs in triacylglycerols and cholesteryl esters, altering neutral lipid unsaturation profiles.
- Impaired LD formation redistributes PUFAs into membrane phospholipids, increasing membrane unsaturation and ferroptosis susceptibility.
- In human lung adenocarcinoma cells, LDs exhibit a dual, context-dependent role in ferroptosis regulation.
- Ferroptosis suppressor protein 1 (FSP1) deficiency amplifies lipid peroxidation within LDs, promoting ferroptosis.
- This study highlights LDs as multifaceted regulators of ferroptosis, linking metabolic and redox quality control mechanisms.