FIGURE 7.

Model of the role of supercomplex formation for the channeling of electrons through the oxidative phosphorylation pathway. A, under standard conditions respirasomes as well as smaller supercomplexes and single complexes are observed simultaneously in the inner mitochondrial membrane. B, dissociation of complex I from the respirasomes supports electron transfer from cytosolic NAD(P)H into the mitochondrial electron transport chain via the external alternative dehydrogenases. Supercomplex dissociation can be induced by acidification of the cell and accumulation of organic acids such as it occurs during hypoxia. These same conditions were previously described to inhibit the enzyme activity of complex I and stimulate activity of the alternative dehydrogenases (45–47). The shift from complex I to the alternative dehydrogenases would support oxidation of cytosolic NADH to keep the glycolytic flux upright when oxidative phosphorylation is reduced upon hypoxia. UQ, ubiquinone; Nd2, alternative NAD(P)H dehydrogenase; AOX, alternative oxidase.