Fig. 9.

Schematic representation of the putative mechanism by which IR leads to ferritinophagy and ferroptosis of intestinal epithelial cells. IR promotes ferritinophagy by upregulating NCOA4, which releases free iron that activates Mfrn2 on the mitochondrial membrane of intestinal epithelial cells. Mfrn2-mediated transportation of cytoplasmic free iron into the mitochondria results in mitochondrial iron overload and excessive ROS production, eventually leading to lipid peroxidation and ferroptosis.