Figure 1.

Reactive oxygen species (ROS) generation and homeostasis. The endogenous generation of ROS is primarily derived from the mitochondrial electron transport chain (ETC), including a family of membrane-bound NADPH oxidases (NOXs) and 5-Lipoxygenase (5-LOX). As a precursor of H₂O₂ and OH^•, O₂⁻can be converted into H₂O₂ by three isoforms of superoxide dismutases (SOD) (i.e., SOD1, 2, and 3) that locate in the cytoplasm, mitochondria matrix, and extracellular matrix. O₂⁻ reacts with nitric oxide (NO), and produces peroxynitrite (ONOO⁻), which will decrease antioxidant capacity. OH^• is the production of H₂O₂ undergoing Fenton chemistry, and it owns the strongest chemistry activity, which can cause damage to biomolecules (such as DNA damage, lipid peroxidation, and protein denaturation). In addition, H₂O₂ can be catalyzed to H₂O by peroxiredoxins (PRXs), glutathione peroxidases (GPXs), and catalase (CAT). Glutathione (GSH) is the main non-enzymatic antioxidant in cells, and plays an important role in the degradation of H₂O₂. Two molecules of GSH are oxidized by H₂O₂ through GPX, and are converted into glutathione disulfide (GSSG), and then are regenerated GSH via glutathione reductase (GR) and NADPH.