STRUCTURE AND ORGANIZATION OF MITOCHONDRIAL RESPIRATORY COMPLEXES: A NEW UNDERSTANDING OF AN OLD SUBJECT.

The enzymatic complexes of the mitochondrial respiratory chain have been extensively investigated in their structural and functional properties. A clear distinction is possible today between three complexes in which the difference in redox potential allows proton translocation (Complexes I, III, and IV) and those having the mere function to convey electrons to the respiratory chain. We also have a clearer understanding of the structure and function of most respiratory complexes, of their biogenesis and regulation, and their capacity to generate Reactive Oxygen Species. Past investigations led to the conclusion that the complexes are randomly dispersed and functionally connected by diffusion of smaller redox components, Coenzyme Q and cytochrome c. More recent investigations by native gel electrophoresis and single particle image processing showed the existence of supramolecular associations. Flux control analysis demonstrated that Complexes I and III in mammals and I, III, and IV in plants kinetically behave as single units, suggesting the existence of substrate channelling. The present review discusses conditions affecting formation of supercomplexes which, besides kinetic advantage, have a role in stability and assembly of the individual complexes and in preventing excess oxygen radical formation. Disruption of supercomplex organization may lead to functional derangements responsible for pathological changes.