Fig. 3: Oxidative phosphorylation, ROS generation, pathology, and redox signaling.

a During oxidative phosphorylation, electron carriers NAD+ and FAD feed electrons to the ETC at either complex I or II. The electrons are shuttled through four membrane-bound protein complexes, referred to as complexes I-IV, which undergo a series of redox reactions. Through this process electrons from complexes I and II also enter the `Q-cycle', where they are passed to another electron carrier, ubiquinone (Q), to facilitate transfer to cytochrome c (via complex III as an intermediary). Diatomic oxygen binds to Complex IV, where it accepts the electrons carried by cytochrome C and is reduced to water. Energy released through these reactions facilitates an electrochemical proton gradient, or mitochondrial membrane potential, within the intermembrane space. To relieve this membrane potential, protons can reenter into the mitochondrial matrix through another protein complex, ATP synthase, which harnesses the mechanical energy generated by the movement of protons to overcome energy constrictions limiting the conversion of adenosine diphosphate (ADP) into ATP. “Leaky" electrons result in the generation of ROS. Adapted from ref. ¹²⁵. b Oxygen is involved in both redox signaling and pathology in the form of ROS. A number of sources, both endogenous and exogenous, are capable of generating cellular ROS. H₂O₂ is involved in the signal transduction of pathways that control cell growth, proliferation, apoptosis, and differentiation. However, most ROS species, particularly HO•-, facilitate oxidative stress, cell damage, inflammation and, subsequently, disease. Figure created with BioRender.com, released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.