Is super-complex organization of the respiratory chain required for optimal electron transfer activity?

The supramolecular assembly of the main respiratory chain enzymatic complexes in the form of “supercomplexes” has been proved by structural and functional experimental evidence. This evidence strongly contrasts the previously accepted Random diffusion Model stating that the complexes are functionally connected by lateral diffusion of Coenzyme Q and cytochrome c. This review provides an analysis of the functional consequences of the intermolecular association of the respiratory complexes pointing out the role of Coenzyme Q and of cytochrome c as channeled or as freely diffusing intermediates in the electron transfer activity of their partner enzymes. The association of Complex I with a Complex III dimer appears to be a common feature of mitochondrial respiratory chains, assuring electron channeling through bound Coenzyme Q, whereas the extent of association of Complex IV appears to depend on the mitochondrial type so that electron transfer often appears to be effected by random diffusion of cytochrome c.