Open questions: respiratory chain supercomplexes-why are they there and what do they do?

Abstract

In the mitochondrial inner membrane the respiratory enzymes associate to form supramolecular assemblies known as supercomplexes. The existence of supercomplexes is now widely accepted-but what functional or structural advantages, if any, do they confer?

Fig. 1

Reactions catalysed by the respirasome supercomplex. The respirasome comprises complexes I, III and IV. Complex I catalyses oxidation of NADH coupled to reduction of ubiquinone-10 to ubiquinol; the entrance to the ubiquinone-binding channel is marked. Complex III (present as a dimer) catalyses reoxidation of ubiquinol, but in a ‘bifurcation’ reactions separates the two electrons that are generated: one is passed to cytochrome c, the other is recycled back across the membrane to reduce a further ubiquinone. Each cycle comprises sequential oxidation of two ubiquinol and reduction of one ubiquinone; the recycling increases the proton-pumping stoichiometry. Cytochrome c is oxidised by complex IV, where the electrons are consumed in reduction of O₂ to water. The same structure is shown in the inset viewed from the matrix side of the membrane. Figure created from the structures of the respirasome from porcine heart mitochondria at 5.4 Å resolution (Gu et al., 2016 [3]) and bovine cytochrome c (6FF5.PDB), with higher-resolution structures for complex I (6G2J.PDB) and inhibitor-bound complex III (1PPJ.PDB) used to mark the flavin and bound Q/QH₂