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