Fig. 1

Mechanism of iron homeostasis and ferroptosis occurrence. (By Figdraw.) In cardiomyocytes, iron uptake is dependent on the endocytosis of TF bound to TFR1. Excess iron is either bound to FTH or exported by FPN; iron can be released by ferritinophagy. An excessive LIP accumulates within cells when iron homeostasis is disrupted, leading to overactivation of the Fenton reaction. AA/AdA-PE undergoes iron-dependent lipid autoxidation or peroxidation through the Fenton reaction leading to the formation of PLOOH that eventually destroy membrane integrity and induce ferroptosis. TF, transferrin; TFR1,transferrin receptor protein 1;STEAP3, metalloreductase STEAP3; DMT1, divalent metal transporter 1; AA, arachidonic acid; AdA, adrenic acid; AA-CoA, arachidonic coenzyme; AdA-PE, adrenic acid-phosphatidylethanolamines; LPCAT3, lysophosphatidylcholine acyltransferase 3; PLOOH, phospholipid hydroperoxides LIP, labile iron pool; SLC39A14, solute carrier family 39 member 14 (ZIP14); FPN, ferroportin; FTH, ferritin; NCOA4, nuclear receptor coactivator 4