Figure 4.

GPx4 counteracts lipid peroxidation

Extracellular cystine is transferred into the cell through the action of the cell membrane glutamate-cystine antiporter system Xc ⁻, then converted to cysteine. Synthesis of reduced glutathione (GSH) from glutamate, cysteine, and glycine is catalyzed by GCL and GSS. GPx4 converts reduced GSH into oxidized glutathione (GSSG), while reducing lipid hydroperoxides (L-OOH) to lipid alcohols (L-OH), preventing the accumulation of lipid peroxides and inhibiting ferroptosis. (Created with BioRender.com). GCL: glutamate-cysteine ligase. GSS: glutathione synthetase. GPx4: glutathione peroxidase 4.