Glutathione Pathway (Ferroptosis Induction)

The glutathione pathway is central to the regulation of ferroptosis, a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation. The pathway’s key components include glutathione (GSH), glutathione peroxidase 4 (GPX4), and system Xc−, which together maintain cellular redox balance and prevent lethal accumulation of lipid reactive oxygen species (ROS). Inhibition or depletion of GSH or GPX4 leads to unchecked accumulation of lipid peroxides, triggering ferroptotic cell death. Key ferroptosis inducers include erastin (blocks system Xc−) and RSL3 (directly inhibits GPX4).

Inhibition of glutathione synthesis or glutathione peroxidase activity, leading to lipid peroxidation and ferroptosis