NRF2-mediated pathway of glutathione synthesis. The expression of antioxidant proteins (blue) can be induced by the Keap1-NRF2 pathway. Cystine introduced into the cytoplasm via xCT (SLC7A11) is converted to cysteine by cystine reductase (CR). Glutamine is converted to glutamate by glutaminase 1 (GLS1). Glutamate and cysteine bind and are transformed to γ-glutamyl-cysteine by glutamate-cysteine ligase (GCL). Glutathione synthetase (GSS) induces glutathione (GSH) synthesis via inducing a covalent bond between γ-glutamyl-cysteine and glycine. Glutathione peroxidase (GPX) oxidizes GSH to GSSG with H2O2 reduction to H2O. GSSG can then be reduced by glutathione reductase (GSR). In addition to the GSH system, the thioredoxin (TRX) system (thioredoxin reductase (TXNRD), thioredoxin (TXN), and peroxiredoxin (PRX)) also comprises NRF2-mediated antioxidant proteins.