Cryo-EM structure and kinetics reveal electron transfer by 2D diffusion of cytochrome c in the yeast III-IV respiratory supercomplex

Significance In the last steps of food oxidation in living organisms, electrons are transferred to oxygen through the membrane-bound respiratory chain. This electron transfer is mediated by mobile carriers, such as membrane-bound quinone and water-soluble cytochrome c . The latter transfers electrons from respiratory complex III to complex IV. In yeast, these complexes assemble into III 2 IV 1/2 supercomplexes, but its role has remained enigmatic. This study establishes a functional role for this supramolecular assembly in the mitochondrial membrane. We used cryo-EM and kinetic studies to show that cytochrome c shuttles electrons by two-dimensional diffusion, sliding along the surface of III 2 IV 1/2 . The structural arrangement of III 2 IV 1/2 supercomplexes suggests a mechanism to regulate cellular respiration.