Inhibition of mitochondrial complex I triggers ROS production, lipid peroxidation and ferroptosis; Melanoma dedifferentiation increases sensitivity to ferroptosis; Depletion of cyst(e)ine and inhibition of system xc− promote lipid peroxidation and ferroptosis; Expression of system xc− is negatively associated with CD8+ T cell signature, IFNγ expression and patient outcome. The gene discussed is CD8A; the disease is melanoma.