Fig. 2

SLC7A11 promotes the oxidative stress response and inhibits ferroptosis. Extracellular cystine is imported into cells through SLC7A11 and converted to cysteine that in turn serves as the rate-limiting precursor for glutathione biosynthesis. Reduced glutathione (GSH) is used as a co-factor by various enzymes involved in ROS detoxification, such as GPX4. Overproduction of lipid hydroperoxides induces ferroptosis. GPX4 uses GSH to detoxify lipid hydroperoxides to lipid alcohols, thus repressing ferroptosis. γGCS γ-glutamylcysteine synthetase, GS glutathione synthetase, GPX4 glutathione peroxidase 4, GST glutathione S-transferase, GR glutathione reductase, Grx glutaredoxin, GSH reduced glutathione, GSSG oxidized glutathione, lipid-OOH lipid hydroperoxide, lipid-OH lipid alcohol Gly glycine