FIG. 4.

Role of iron metabolism in ferroptosis. Excess iron results in the Fenton reaction producing ROS. Iron transport proteins such as DMT1, transferring, and TfR promote ferroptosis. DMT1 imports iron from the apical lumen side into duodenal enterocytes. Transferrin and its receptor, TfR, mediate the transport of iron through blood. NCOA4 mediates the breakdown of ferritin to release free iron, thus promoting ferroptosis. Iron storage (ferritin) and export (ferroportin) proteins inhibit ferroptosis by sequestering iron and decreasing cellular iron levels. DMT1, divalent metal transporter-1; NCOA4, nuclear receptor coactivator 4; TfR, transferrin receptor.