The role of ferroptosis in organ toxicity

Ferroptosis, an iron-dependent form of programmed cell death, is characterized by iron overload, increased reactive oxygen species (ROS) generation, and depletion of glutathione (GSH) and lipid peroxidation. Lipophilic antioxidants and iron chelators can prevent ferroptosis. GSH-dependent glutathione peroxidase 4 (GPX4) prevents lipid ROS accumulation. Ferroptosis is thought to be initiated through GPX4 inactivation. Moreover, mitochondrial iron overload derived from the degradation of ferritin is involved in increasing ROS generation. Ferroptosis has been suggested to explain the mechanism of action of organ toxicity induced by several drugs and chemicals. Inhibition of ferroptosis may provide novel therapeutic opportunities for treatment and even prevention of such organ toxicities.

Automated summary

Ferroptosis is an iron-dependent form of programmed cell death characterized by iron overload, increased ROS generation, and depletion of GSH and lipid peroxidation. Inhibition of ferroptosis may provide novel therapeutic opportunities for treating and preventing organ toxicities induced by drugs and chemicals. Ferroptosis is initiated through GPX4 inactivation and mitochondrial iron overload, leading to increased ROS generation.