Supercomplexes in the respiratory chains of yeast and mammalian mitochondria

Around 30-40 years after the first isolation of the five complexes of oxida tive phosphorylation from mammalian mitochondria, we present data that fund amentally change the paradigm of how the yeast and mammalian system of oxid ative phosphorylation is organized. The complexes are not randomly distribu ted within the inner mitochondrial membrane, but assemble into supramolecul ar structures. We show that all cytochrome c oxidase (complex IV) of Saccha romyces cerevisiae is bound to cytochrome c reductase (complex III), which exists in three forms: the free dimer, and two supercomplexes comprising an additional one or two complex IV monomers, The distribution between these forms varies with growth conditions. In mammalian mitochondria, almost all complex I is assembled into supercomplexes comprising complexes I and III a nd up to four copies of complex IV, which guided us to present a model for a network of respiratory chain complexes: a 'respirasome'. A fraction of to tal bovine ATP synthase (complex V) was isolated in dimeric form, suggestin g that a dimeric state is not limited to S.cerevisiae, but also exists in m ammalian mitochondria.