Biogenesis of Cytochrome c Complexes: From Insertion of Redox Cofactors to Assembly of Different Subunits

Cytochromes (cyts) are ubiquitous heme containing proteins that are key components of energy transduction pathways. They participate in a wide variety of electron transfer reactions, which are essential for cellular processes responsible for chemical energy (ATP) production. The cbb3-type cyt c oxidase (cbb3-Cox) provides an excellent model to study biogenesis of membrane-integral, oligomeric cyt c complexes. Its subunits contain three hemes c, two hemes b and a copper (CuB) atom as cofactors that use distinct insertion processes. In cyts c, heme b is covalently ligated (referred to as heme c) via a complex maturation process that involves in some species up to nine components (Ccm-System I). In addition to the cyts c, many cyt c containing complexes carry other cofactors, and insertion of these cofactors requires additional biogenesis components besides the Ccm-system I. In the case of cbb3-Cox, the mechanisms underlying incorporation of hemes b into the catalytic subunit are not well understood. However, remarkable progress was achieved recently on how the single CuB atom at the catalytic heart of this heme-copper oxidase is acquired. Finally, insertion of the cofactors must be temporally and spatially coordinated with the assembly of the subunits in order to yield a functional cbb3-Cox enzyme. In this chapter, we discuss the biogenesis of cbb3-Cox from the insertion of its catalytic heme-copper (CuB) center and maturation of its c-type cyts to the assembly of its mature subunits, mainly focusing on studies carried out with the anoxygenic phototrophic bacterium Rhodobacter capsulatus.