mTOR-Mediated Antioxidant Activation in Solid Tumor Radioresistance

Figure 2

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.