FIGURE 2.

The overview of ferroptosis. This figure shows five systems regulating ferroptosis. The first one is the anti-oxidative GSH-GPX4 pathway, in which system xc⁻, transsulfuration way, GSH and GPX4 involve. The second one is the mevalonate pathway, where CoQ₁₀ is produced. The third one is iron metabolism, where the Fenton reaction happens and the starter of lipid peroxidation, OH^., is produced. The fourth one is mitochondria, on whose membrane oxidative CoQ₁₀ is catalyzed into reductive CoQ₁₀ (CoQ₁₀H₂) and DHODH could inhibit this process. Meanwhile, the increased ROS along with the increased TCA cycle may help ferroptosis. The fifth one is lipid metabolism, in which PUFA is catalyzed into peroxidative lipid finally. GSH, glutathione; GSSG, glutathione disulfide; GSR, glutathione-disulfide reductase; FSP1, ferroptosis suppressor protein-1; GPX4, glutathione peroxidase 4; HMG-CoA, 3-hydroxy-3-methyl glutaryl coenzyme A; IPP, isopentenyl pyrophosphate; FPP, farnesyl pyrophosphate; TF, transferrin; TFRC, transferrin receptor; STEAP3, six-transmembrane epithelial antigen of prostate 3; DMT1, divalent metal transporter 1; LIP, labile iron pool; TCA cycle, Tricarboxylic Acid cycle; DHODH, dihydroorotate dehydrogenase; ROS, reactive oxygen species; PUFA, polyunsaturated fatty acids; PE, phosphatidylethanolamine; ACSL4, acyl-CoA synthetase long-chain family member 4; LPCAT3, lysophospholipid acyltransferase 3; LOX, lipoxygenase.