The selenoprotein glutathione peroxidase 4 (GPX4) is a master regulator of ferroptosis, a form of programmed cell death induced by iron-dependent lipid peroxidation. GPX4 converts lipid hydroperoxides to non-toxic lipid alcohols, therefore preventing ferroptosis. Research studies show that selenium enhances GPX4 expression and inhibits ferroptotic death to protect neurons. In addition, some therapy-resistant cancer cells depend on GPX4 to survive. Loss of GPX4 leads to ferroptosis and thus prevents tumor relapse in mice. Furthermore, redox homeostasis mediated by GPX4 is essential for activation of the cytosolic DNA-sensing cGAS-STING pathway and initiation of the subsequent innate immune response.
