Two cellular antioxidant defenses. (A) The upper panel showing protein and non-protein thiols as the first-line antioxidant defense. Increasing concentrations of ROS cause protein cysteinyl oxidation from thiol to sulfenic acid, sulfinic acid and sulfonic acid. If unrepaired, the structure and activity of oxidized protein are affected. However, cells have evolved reducing systems (TXN, TXNRD1 and SRXN1) to recover from sulfenic acid and sulfinic acid. Any impairments of the reducing enzymes or cofactor NADPH production decrease the cellular antioxidant buffering capacity. (B) The below panel showing proteasome and autophagy as the second-line antioxidant defense. Proteasome removes oxidized proteins. Autophagy is responsible for removal of large junks such as protein aggregates, damaged organelles, and invading pathogens, beside oxidized proteins. ox in pink cycle: oxidative modification.