Figure 1.

Regulation of iron homeostasis in ferroptosis. HEPH and CP can transform the Fe²⁺ to Fe³⁺, which will be transferred into the cell through TFRC. The cellular Fe³⁺ will be reduced to Fe²⁺ by the STEAP3, which was then transported to the cytoplasm through DMT1. Excess Fe²⁺ generates ROS through the fenton reaction in cell, which could also be transferred out to the cell through Fpn. The binding of hepcidin to Fpn after translation will cause the degradation of Fpn to inhibit the output of iron. The combination of IRP1/2 and IREs could reduce TFRC expression to induce ferritin expression. PCBP1/2 are responsible for the transportation of iron to ferritin, NCOA4 could mediate autophagy of ferritin. FtMt could regulate the content of Fe²⁺ and ROS through VDAC2/3 and NOX2.