Figure 7.
The mechanism of GSH depletion in induction of ferroptosis. Lipid-OOHs can be formed by autoxidation via Fenton reaction or by enzymatic reaction via lipoxygenases (LOXs). Lipid-OOHs are regulated by the balance between the activities of GPX4 and LOXs or Fenton reaction. System Xc− impairment or GPX4 inactivation leads to Lipid-OOH accumulation which cannot be effectively cleared under the loss of GPX4 activity. Ultimately, the accumulation of Lipid-OOH triggers ferroptosis. Ferroptosis can be inhibited by DFO, liproxstatin-1 (Lip-1), and ferrostatin-1 (Fer-1).