A structural model of the cytochrome c reductase/oxidase supercomplex from yeast mitochondria

Abstract

Mitochondrial respiratory chain complexes are arranged in supercomplexes within the inner membrane. Interaction of cytochrome c reductase (complex III) and cytochrome c oxidase (complex IV) was investigated in Saccharomyces cerevisiae. Projection maps at 15 Å resolution of supercomplexes III 2 + IV1 and III2 + IV2 were obtained by electron microscopy. Based on a comparison of our maps with atomic x-ray structures for complexes III and IV we present a pseudo-atomic model of their precise interaction. Two complex IV monomers are specifically attached to dimeric complex III with their convex sides. The opposite sides, which represent the complex IV dimer interface in the x-ray structure, are open for complex IV-complex IV interactions. This could lead to oligomerization of III 2 + IV2 supercomplexes, but this was not detected. Instead, binding of cytochrome c to the supercomplexes was revealed. It was calculated that cytochrome c has to move less than 40Å at the surface of the supercomplex for electron transport between complex III2 and complex IV. Hence, the prime function of the supercomplex III2 + IV2 is proposed to be a scaffold for effective electron transport between complexes III and IV. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.