The initiation of ferroptosis involves the failure of the cell's antioxidant defenses, particularly the glutathione (GSH) system and glutathione peroxidase 4 (GPX4). When glutathione levels are depleted or GPX4 is inactivated, toxic lipid peroxides accumulate, leading to cell death. Iron plays a crucial role by catalyzing the formation of reactive oxygen species (ROS) through the Fenton reaction, further exacerbating oxidative damage.
