Chapter 12: Respiratory Supercomplexes in Mitochondria

This chapter discusses the supramolecular organization of the mitochondrial respiratory chain. Clear experimental evidence has ascertained that the major respiratory complexes involved in energy conservation are assembled as supramolecular units (supercomplexes, or SCs) in stoichiometric ratios. The functional role of SCs is less well defined, and still open to discussions and controversies. Several lines of evidence are presented favouring the concept that electron transfer from Complex I to Complex III is operated by channelling of electrons through Coenzyme Q molecules bound to the SC I+III, in contrast with the alternative 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 associated in SCs. Furthermore, another property provided by the supercomplex assembly is the control of generation of reactive oxygen species by Complex I. The chapter also discusses the physiological and pathological implications of the supercomplex assembly of the respiratory chain.