Fig. 2

Metabolic pathways in ferroptosis. In the process of ferroptosis, lipid peroxidation plays a key role in triggering ferroptosis. A great number of molecules participate in ferroptosis by regulating the same protein, resulting in similar downstream pathways. For example, p53, BAP1, ATF3, phosphorylated BECN1,and the combination of erastin and SLC7A5, inhibit expression or activation of SLC7A11, which leads to the depletion of cysteine and GSH in cells. Some other molecules such as FINO2 and RSL3 inhibit GPX4 in cells. The decrease of GSH or GPX4 in cells contributes to lipid peroxidation, ultimately resulting in ferroptosis. MIR137 inhibits SLC1A5 and decreases Gln, Glu, and α-KG in cells, also involved in ferroptosis. The cadherin–NF2–Hippo–YAP signaling axis is involved in ferroptosis. miRNA-17-92 prevents ferroptosis in cells through targeting the A20-ACSL4 axis. ACSL4 that is also regulated by Sp1 regulates the expression of 5-HETE and long polyunsaturated ω6 fatty acids in cells, thus participating in the regulation of ferroptosis