Fig. 7
From: Research progress on multiple cell death pathways of podocytes in diabetic kidney disease
Ferroptosis-related pathway. Glutamate inhibits cystine uptake by the cystine-glutamate antitransporter (system Xc−), which subsequently leads to glutathione (GSH) depletion and the inactivation of the phospholipid peroxidase glutathione peroxidase 4 (GPX4), which promotes the accumulation of H2O2, and NOX4, which also promotes the accumulation of H2O2. Both eventually lead to ferroptosis. In addition, dysfunction of iron metabolism in cells can also lead to ferroptosis. The intracellular iron level is mainly regulated by transferrin receptor (TFR), and the increase of TFR expression will cause more Fe3+ to enter the cell, and Fe3+ will be reduced to Fe2+ by iron reductase, and the production of ROS will be promoted through Fenton reaction, which ultimately leads to ferroptosis