Novel insights into the mechanism of electron transfer in mitochondrial cytochrome c

Abstract The supramolecular arrangement of respiratory complexes into supercomplexes is widely accepted. The common feature observed in the supercomplex architecture from organisms of diverse phylogenetic origin is the reduction of the distance between cytochrome bc1 (complex III) and cytochrome c oxidase (complex IV). Such an arrangement reduces the dimensionality (from 3D to 2D) of the diffusional search of cytochrome c as the electron carrier that connects both complexes. In this scenario, our recent finding of additional binding sites for cytochrome c reinforces the concept of a “restrained 2D sliding pathway” onto the supercomplex surface. Herein, we analyze novel mechanistic insights into electron transfer towards cytochrome c, including modulation of the redox potential by physical contact as well as gated, long-range electron transfer through an aqueous solution. These data establish a new horizon for the understanding of electron transfer mechanisms beyond unique and well-orientated protein complexes. Multiple and dynamic long-distance conformational ensembles compatible with electron transfer could indeed contribute to the rapid adjustment of electron flow in response to changing cellular conditions.