Figure 4.

Proposed mechanism for cardiac iron overload related to postconvulsive hypoxia-ischemia. Iron transported by holotransferrin is recognized by the plasma membrane receptor (Trf-R). After endocytosis, Fe³⁺ is reduced to Fe²⁺ in endosomes by the metalloreductase six-transmembrane epithelial antigen of prostate 3 (Steap3) and released from endosomes by divalent metal transporter 1 (DMT1). After the Fenton reaction, iron promotes lipid peroxidation via the activation of lipoxygenases, resulting in hemosiderin accumulation. On the other hand, the axis composed of the cystine/glutamate antiporter system X_c, Glutation (GSH) and Glutation peroxidase 4 (GPX4) is as a key regulator for tissue iron overload and ferroptosis. Other possible mechanisms of cardiomyocyte death are listed on the left side of the picture.