Structure and Mechanism of Respiratory III–IV Supercomplexes in Bioenergetic Membranes

In the final steps of energy conservation in aerobic organisms, free energy from electron transfer through the respiratory chain is transduced into a proton electrochemical gradient across a membrane. In mitochondria and many bacteria, reduction of the dioxygen electron acceptor is catalyzed by cytochrome c oxidase (complex IV), which receives electrons from cytochrome bc 1 (complex III), via membrane-bound or water-soluble cytochrome c . These complexes function independently, but in many organisms they associate to form supercomplexes. Here, we review the structural features and the functional significance of the nonobligate III 2 IV 1/2 Saccharomyces cerevisiae mitochondrial supercomplex as well as the obligate III 2 IV 2 supercomplex from actinobacteria. The analysis is centered around the Q-cycle of complex III, proton uptake by Cyt c O, as well as mechanistic and structural solutions to the electronic link between complexes III and IV.