FIG. 3.
Mechanisms governing ferroptosis. Ferroptosis is an iron-dependent regulated cell death pathway based on the accumulation of lipid peroxides. The primary regulators of this pathway are GPX4 and cystine/glutamate antiporter System Xc−. GPX4 reduces cytotoxic lipid ROS, while System Xc− transports the cystine, the necessary precursor for substrates of GPX4. Additional pathways include ACSL4, which incorporates PUFA-CoA into phospholipid cell membranes, and FSP1, which reduces lipid ROS through a GPX4-independent pathway. ACSL4, acyl-CoA synthetase long-chain family member 4; FSP1, ferroptosis suppressor protein 1; GPX4, glutathione peroxidase 4; PUFA, polyunsaturated fatty acid.