Fig. 5.

Targeting ferroptosis in lipid metabolism pathways. Cellular fatty acids are taken up by CD36 and FABPs, and stored in the free fatty acid (FFA) pool. Cells can also take up cholesterol via the LDLR or produce it from acetyl-CoA. These fatty acids can then be elongated to form long fatty acids and can be unsaturated to form monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs). MUFAs can be converted to PUFAs via the activity of FADS. ACSL4 and LPCAT3 are key enzymes that promote the incorporation of PUFAs into phospholipids (PLs) to form PL-PUFAs and induce ferroptosis. Molecules in the pink and green text boxes inhibit or induce, respectively, the indicated components in the lipid metabolism regulatory pathways, thereby suppressing or triggering, respectively, ferroptosis. ACC acetyl-CoA carboxylase, ACSL4 acyl-CoA synthetase long-chain family member 4, ALOX arachidonate lipoxygenase, CD36 cluster differentiation 36, FABP fatty acid binding protein, FADS fatty acid desaturase, FASN fatty acid synthase, HMG-CoA 3-hydroxy-3-methylglutaryl-CoA, HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase, LDLR low density lipoprotein receptor, LPCAT3 lysophosphatidylcholine acyltransferase 3, PEBP1 phosphatidylethanolamine binding protein 1, SCD1 stearoyl-coenzyme A desaturase 1, SQLE squalene epoxidase, SQS squalene synthase. Created with BioRender.com