Fig. 1.

Overview of the ferroptosis pathways. Ferroptosis occurs as a result of the production of large amounts of lipid peroxides by the Fenton reaction. Elevated intracellular iron concentration or the disruption of cystine transport leads to a depletion of the antioxidant GSH; the lower level of GPX4 activity causes increased accumulation of ROS that consequently leads to lipid peroxidation and triggers ferroptosis. AA, arachidonic acid; Fe²⁺, ferrous iron; DMT1, divalent metal transporter 1; Fe³⁺, ferric iron; Fpn, ferroportin; GPX4, glutathione peroxidase 4; GSH, glutathione; GSSG, glutathione disulfide; NCOA4, nuclear receptor coactivator 4; PUFA, plasma membrane unsaturated fatty acid; ROS, reactive oxygen species; SLC3A2, solute carrier family 3 member 2; SLC7A11, solute carrier family 7 member 11; Tf, transferrin; TfR, transferrin receptor