Figure 3.

Redox regulation of ferroptosis. Ferroptosis is driven by lipid peroxidation, which is catalyzed by redox-active iron. Cysteine availability, which is regulated by cystine uptake via system x_c^- or through the transsulfuration pathway, is essential for efficient synthesis of GSH. GPX4 utilizes GSH to reduce lipid hydroperoxides, thereby suppressing ferroptosis. GSSG is reduced to GSH by GR using NADPH. In addition, reduced coenzyme Q (CoQH₂) acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxidation. The CoQ oxidoreductase ferroptosis suppressor protein 1 (FSP1) maintains CoQH₂ levels and acts parallel to GPX4 to inhibit ferroptosis. FSP1, ferroptosis suppressor protein 1; GSH, glutathione; GPX4, glutathione peroxidase 4; GSSG, glutathione disulfide; GR, glutathione reductase.