Fig. 1: Mitochondrial oxidative phosphorylation.
Nutrients are oxidized in mitochondrial matrix to generate a transmembrane electrochemical gradient, which is used for ATP synthesis, whose thermodynamic driving is maintained by ANT. Complexes I and II oxidize NADH and FADH2, respectively, which are generated by the oxidation of energy substrates in the tricarboxylic acid (TCA) cycle. Electrons (2e-) are transferred along the electron transport chain (ETC), due to increasing redox potentials of mitochondrial complexes. The energy released is used by Complexes I, III, and IV to pump protons into the intermembrane space (IMS), generating a proton gradient—also known as the protonmotive force—across the inner mitochondrial membrane. Energy derived from re-entry of protons into the matrix via ATP synthase (Complex V) drives ATP synthesis. The adenine nucleotide translocase (ANT) facilitates the exchange of matrix-derived ATP for cytosolic ADP, maintaining the ATP synthesis reaction far from thermodynamic equilibrium. IMS: intermembrane space. See main text for additional abbreviations. Image adapted from Servier Medical Art (https://smart.servier.com/), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).
