Coenzyme Q and respiratory supercomplexes: physiological and pathological implications

It was discovered over 60 years ago that the mitochondrial respiratory chain is constituted of a series of protein complexes imbedded in the inner mitochondrial membrane. Experimental evidence has more recently ascertained that the major respiratory complexes involved in energy conservation are assembled as supramolecular units (supercomplexes, SCs) in stoichiometric ratios. The functional role of SCs is less well defined, and still open to discussion. Several lines of evidence favour the concept that electron transfer from Complex I to Complex III operates by channelling of electrons through Coenzyme Q molecules bound to the SC I1III2IVn, in contrast with the previously accepted hypothesis that the transfer of reducing equivalents from Complex I to Complex III occurs via random diffusion of the Coenzyme Q molecules in the lipid bilayer. On the contrary, electron transfer from Complex III to Complex IV seems to operate, at least in mammals, by random diffusion of cytochrome c molecules between the respiratory complexes even if assembled in SCs. Furthermore, another property provided by the supercomplex assembly is the control of generation of reactive oxygen species by Complex I, that might be important in the regulation of signal transduction from mitochondria. This review discusses physiological and pathological implications of the supercomplex assembly of the respiratory chain.