What is the major intracellular source of ROS?

The mitochondria is the major intracellular source of ROS. Of the total mitochondrial oxygen consumed, 1-2% is used for the formation of ROS. During the process of oxidative phosphorylation, electron leakage occurs from the electron transport chain and interacts with oxygen, causing the production of superoxide radicals as a byproduct. Electron leakage occurs primarily at the level of complex I and complex III of the respiratory chain, and is thought to be species and tissue dependent. The superoxide radicals can then be converted into other ROS like hydroxyl radicals (OH) and hydrogen peroxide (H202). In addition to the mitochondria, NADPH oxidases are another important intracellular source of ROS. NADPH oxidases generate ROS as part of their physiological process. They catalyze the transfer of electrons from NADPH to molecular oxygen through the Nox catalytic subunit to generate ROS.