Fig. 1. Regulating pathways of ferroptosis.

TFR1 triggers iron uptake, which is regulated by MYCN and YAP pathways. Accumulation of iron facilitates lipid peroxidation and ferroptosis. In contrast, SLC7A11/GPX4 axis prevents ferroptosis by antioxidant role. SLC7A11 or GPX4 expressions are regulated by multiple regulators including NRF2, SOX2, TAZ, EST1, and SREBP-1a etc. Moreover, SLC7A11 mediates cystine uptake, subsequently, activates Rag-mTORC1-4EBP pathway-induced GPX4 protein synthesis. Ferroptosis resistance is blocked by some mediators such as p53, KLF2 etc. In addition to GPX4, FSP1 is a ferroptosis inhibitor by inhibiting lipid ROS accumulation, which is reversed by KEAP1/NRF2 signaling pathway.