Fig. 2.

Regulation of ferroptosis. A SIGMAR1 interacts with ITPR to facilitate calcium exchange between the endoplasmic reticulum (ER) and mitochondria, promote lipid droplet catabolism, and enhance sensitivity to ferroptosis. Moreover, the PACS2, HSPA9/VDAC1 complex also mediates the transmission of ferroptosis signals from the ER to mitochondria. B CA9 inhibits ferroptosis through the AMPK pathway or by directly inducing alkalinization of intracellular pH. Additionally, HIF1A-dependent lactate accumulation inhibits ferroptosis via a pH-dependent mechanism. C Intestinal flora secretes metabolites such as IDA, CAT, or daidzein to modulate the expression of AIFM2 or GPX4 and suppress ferroptosis. D Cancer cells utilize the macropinocytosis pathway to uptake proteins like extracellular albumin to supplement cysteine and inhibit ferroptosis under conditions of system xc- inhibition. Moreover, albumin may directly inhibit lipid peroxidation