Fig. 4: Ferroptosis and cholesterol metabolism.
From: Metabolism-regulated ferroptosis in cancer progression and therapy
Cholesterol synthesis is catalyzed by a series of enzymes, such as HMGCR, SQS and SQLE, via MVA pathway. SREBP2 regulates the expression of HMGCR and the levels of TF, which inhibits lipid peroxidation and ferroptosis. MVA pathway can regulate the synthesis of GPX4 and CoQ, which are the negative regulators in ferroptosis. Besides, cholesterol in the tumor microenvironment can increase the expression of CD36 in tumor-infiltrating CD8+ T cells, which can increase FA uptake and promote lipid peroxidation, thus inducing ferroptosis in CD8+ T cells and maintaining the survival of cancer cells. HMG-CoA 3-hydroxy-3-methylglutaryl-CoA, HMGCR HMG-CoA reductase, MVA mevalonic acid, IPP isopentenyl pyrophosphate, FPP farnesyl pyrophosphate, SQS squalene synthase, FIN56 ferroptosis inducer 56, SQLE squalene epoxidase, SIM simvastatin, ART artesunate, SREBP2 sterol responsive element binding protein 2, TF transferrin, GPX4 glutathione peroxidase 4, PLOOH phospholipid hydroperoxides, PLOH phospholipid alcohols, CoQ ubiquinone, CoQH2 ubiquinol, NADPH reduced nicotinamide adenine dinucleotide phosphate (Created with BioRender.com).
