FIGURE 2.

Ferroptosis metabolic pathway. (A) Antioxidant metabolism. GPX4 and CoQ10 are two parallel pathways of antioxidant metabolism. GPX4 exerts an antioxidant function through the metabolism of GSH. CoQ10 is reduced to CQ₁₀H₂ under the action of FSP1, inhibiting lipid peroxidation by capturing lipid peroxidation free radicals. (B) Iron metabolism. Iron binds to TF and is released into the cytoplasm by TFRC. Ferritin releases a large amount of iron‐by‐iron autophagy mediated by NACO4. Heme releases iron under the catalysis of HO‐1. FPN can transport iron from cells to the blood. (C) Lipid metabolism signaling pathway. AA/AdA is converted into polyunsaturated fatty acids (PE‐AA) by ACSL4 and LPCAT3. The balance between lipid synthesis, storage, and degradation can also manipulate the ferroptosis process. Acetyl‐CoA can also produce PUFA under the action of ACC synthase, immediately produce a large amount of ROS under the action of Fe²⁺ and LOX15. Abbreviations: GPX4, glutathione peroxidase 4; CoQ10, ubiquinone; FSP1, ferroptosis inhibitor protein 1; TF, transferrin; TFRC, transferrin receptor 1; HO‐1, heme oxygenase‐1; NFS1, cysteine desulfurase 1; ACSL4, acyl‐CoA synthetase 4; AA, arachidonic acid; AdA, epinephrine; LPCAT3, lysophosphatidylcholine acyltransferase 3; ATG5, autophagy‐related 5; BACO4, ###; BH4, tetrahydrobiopterin; Cys, Cysteine; DMT1, divalent metal transporter; FPN, ferroportin; GCLC, glutamate‐cysteine ligase catalytic subunit; Gln, Glutamine; Glu, Glutamate; GR, gluathione reductase; GSH, glutathione; GSS, Glutathione synthetase; GSSH, glutathione counterpart; iFSP1, Inhibit FSP1; iNFS1, Inhibit NFS1; LOX15, lipoxygenase 15; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, NADPH oxidase; PE, Phosphatidylethanolamine; RAB7A, a small GTPase of the Rab family; SLC3A2, solute carrier family 3 member 2; SLC7A11, cystine/glutamate antiporter solute carrier family 7 member 11; STEAP3, Six‐transmembrane epithelial antigen of the prostate 3