Eukaryotic cytochrome c oxidase (CcO), the terminal component of the mitochondrial electron transport chain is a heterooligomeric complex that belongs to the superfamily of heme-copper containing terminal oxidases. The enzyme, composed of both mitochondrially and nuclear encoded subunits, is embedded in the inner mitochondrial membrane, where it catalyzes the transfer of electrons form reduced cytochrome c to dioxygen, coupling this reaction with vectorial proton pumping across the inner membrane. Due to the complexity of the enzyme, the biogenesis of CcO involves a multiplicity of steps, carried out by a number of highly specific gene products. These include mainly proteins that mediate the delivery and insertion of copper ions, synthesis and incorporation of heme moieties and membrane-insertion and topogenesis of constituent protein subunits. Isolated CcO deficiency represents one of the most frequently recognized causes of respiratory chain defects in humans, associated with severe, often fatal clinical phenotype. Here we review recent advancements in the understanding of this intricate process, with a focus on mammalian enzyme.

Department of Pediatrics 1st Faculty of Medicine Charles University Prague Czech Republic