(A) ATP is generated by oxidative phosphorylation conducted by the four RC complexes (CI–CIV) and ATP synthase (CV) located in the inner mitochondrial membrane. Energy released by the electron transfer from NADH and FADH₂ to O₂ is used to pump protons (H⁺) via CI, CIII, and CIV. The proton gradient across the inner mitochondrial membrane drives ATP production via ATP synthase. The proton gradient can be dissipated by re-entry of protons to the mitochondrial matrix through uncoupling proteins (UCPs), which leads to uncoupling of respiration and ATP synthesis. (B) ROS are formed as a byproduct of oxidative phosphorylation. Superoxide is an abundant ROS in the cell and is generated by CI and CIII. Cells protect themselves from oxidative damage by expressing a variety of antioxidant enzymes that convert ROS into less harmful byproducts. Superoxide anion is converted to hydrogen peroxide by manganese SOD. Hydrogen peroxide is then converted to water by glutathione peroxidase, the most abundant peroxidase in the cytosol and mitochondria. Even though hydrogen peroxide is not substantially harmful for the cell, it can be converted to the highly reactive hydroxyl radical (OH^•) in the presence of transition metals via the Fenton reaction. CytC, cytochrome C; CoQ, coenzyme Q10.