Fig. 1. Simplified model for the process of COX assembly.
General chaperones and RNA-specific translational activators (not depicted here but see explanation in the text) are required for synthesis of the mtDNA-encoded subunits forming the core. Following their insertion into the inner membrane, Cox1 and Cox2 are matured by addition of metal cofactors. At some point, substrate-specific chaperones bind Cox1 and Cox2 to maintain them in an assembly-competent state. A predicted Cox3 chaperone has not been yet identified. Following Cox1 maturation, the nuclear DNA-encoded Cox5 and 6 subunits are added to Cox1 prior incorporation of the other core subunits and the rest of the accessory subunits to form the holoenzyme.