ABSTRACT
According to the chemiosmotic energy transduction concept, respiring mitochondria generate an H+ electrochemical gradient (∆µH+) across the inner membrane. This occurs when electrons pass along the electron transport chain that consists of respiratory enzyme complexes made of electron carriers. These complexes have a specific orientation in the membrane in order to carry out the vectorial net H+ movement outward from the mitochondria during the oxidoreduction reactions. The ATP synthase uses the H+ gradient to make ATP inside the mitochondria with stoichiometric uptake of external H+. Thus, the energy released by the redox reaction is first transferred into a transmembrane H+ gradient and then trapped by the synthesis of ATP. The overall energy conservation requires that redox reactions and ATP hydrolysis are coupled to H+ pumping; thus, the ATP synthase is a reversible H+-translocating ATPase. If one chemical reaction occurs without H+ pumping, the energy conservation is abolished and the redox Gibbs free energy is dissipated. As the H+ gradient links respiration and phosphorylation, this implies that protons pumped out by the respiratory complexes and used by ATP synthase are free to diffuse in the aqueous phases. Thus, a so-called delocalized proton circuit exists, requiring the inner mitochondrial membrane to have a low H+ conductance to avoid short-circuiting, i.e., breaking the energetic coupling between the ATP synthase and the respiratory H+ pumps. As this coupling is indirect, the H+ gradient may be diverted to drive other processes such as ion transport systems and heat production. Numerous carriers exist in the inner membrane to allow reducing metabolites to enter the matrix space and to integrate metabolism of mitochondria and cytoplasm (Fig. 1).
