Coa3 and Cox14 are essential for cytochrome c oxidase assembly and negative feedback regulation of COX1 translation in mitochondria

The assembly of the cytochrome c oxidase in the mitochondrial inner membrane is a highly sophisticated process. It requires more than 20 auxiliary proteins to build a functional enzyme, consisting of 11 structural subunits in the yeast Saccharomyces cerevisiae. These structural proteins are of dual genetic origin and assemble in a barely understood process. It has become clear that the mitochondria-encoded subunits are the starting points, to which nuclear-encoded subunits are added in a sequential manner. One of these starting points is Cox1, the central subunit of the enzyme that, together with Cox2, carries the non-proteinaceous cofactors of the active center. Expression of Cox1 has to be tightly regulated in order to prevent the generation of reactive oxygen species by an incomplete enzyme.

We have identified a novel assembly factor, Coa3, that is involved in the early steps of Cox1 biogenesis. Coa3 associates with newly synthesized Cox1 to form a complex together with Cox14. This complex is able to sequester the translational activator Mss51 in order to stop Cox1 translation. Hence, Mss51 exists in equilibrium between a latent, translational resting, and a committed, translation effective, state that are represented as distinct complexes. Full inactivation of the sequestered Mss51 requires Coa1, which associates with the Coa3-Cox14-Cox1-Mss51 complex. Identification of the novel assembly factor Coa3 sheds new light on the early steps of Cox1 biogenesis and the process of sensing unassembled Cox1 for translational regulation.