Figure 1.

ROS axis: generation and detoxification of common reactive oxygen species. The mitochondrial electron transport chain (ETC) and NADPH oxidases (NOX) take up oxygen (O₂) and generate superoxide (O₂^•−) which is dismutated in the mitochondria, peroxisome and endoplasmic reticulum by Copper-Zinc (Cu-Zn) and Manganese (Mn) superoxide dismutases (SOD) to generate hydrogen peroxide (H₂O₂). H₂O₂ is converted into water by simultaneous oxidation of the catalytic cysteine residues of the peroxiredoxin (PRDX) and thioredoxin (TXN) proteins. H₂O₂ is also actively nullified by the glutathione peroxidase-glutathione reductase (GPX-GSR) that recycles oxidized glutathione (GSSG, not shown) back to its reduced form (GSH, not shown). Mitochondrial O₂^•− radicals release Fe⁺ ions by damaging ETC complexes. In presence of Fe²⁺ ions H₂O₂ converts to hydroxyl radical (^•OH) through Fenton’s reaction. Both H₂O₂ and ^•OH interacts and oxidizes macromolecules, alters cellular signaling and causes oxidative DNA damage, which drives gene mutations. ^•OH initiates oxidation of lipids to alkyl (R^•) groups, which then oxidize to alkoxyl (RO^•) and peroxyl (ROO^•) radicals. (ROS is shown in red, dotted blue arrows indicate the source of ROS and purple numbers indicate half-life of these radicals in seconds).