title: Assembly factors and ATP-dependent proteases in cytochrome c oxidase biogenesis.
abstract: Eukaryotic cytochrome c oxidase (CcO), the terminal enzyme of the energy-transducing mitochondrial electron transport chain is a hetero-oligomeric, heme-copper oxidase complex composed of both mitochondrially and nuclear-encoded subunits. It is embedded in the inner mitochondrial membrane where it couples the transfer of electrons from reduced cytochrome c to molecular oxygen with vectorial proton translocation across the membrane. The biogenesis of CcO is a complicated sequential process that requires numerous specific accessory proteins, so-called assembly factors, which include translational activators, translocases, molecular chaperones, copper metallochaperones and heme a biosynthetic enzymes. Besides these CcO-specific protein factors, the correct biogenesis of CcO requires an even greater number of proteins with much broader substrate specificities. Indeed, growing evidence indicates that mitochondrial ATP-dependent proteases might play an important role in CcO biogenesis. Out of the four identified energy-dependent mitochondrial proteases, three were shown to be directly involved in proteolysis of CcO subunits. In addition to their well-established protein-quality control function these oligomeric proteolytic complexes with chaperone-like activities may function as molecular chaperones promoting productive folding and assembly of subunit proteins. In this review, we summarize the current knowledge of the functional involvement of eukaryotic CcO-specific assembly factors and highlight the possible significance for CcO biogenesis of mitochondrial ATP-dependent proteases.
authors.affiliation: Charles University in Prague, First Faculty of Medicine, Department of Pediatrics, Prague, Czech Republic. Lukas.Stiburek@lf1.cuni.cz
authors.forename: Lukas
authors.initials: L
authors.lastname: Stiburek
authors.forename: Jiri
authors.initials: J
authors.lastname: Zeman
mesh_terms: D049069:ATP-Dependent Proteases / Q000378:metabolism*; D000818:Animals; D003576:Electron Transport Complex IV / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D021122:Protein Subunits; D003576:Electron Transport Complex IV; D049069:ATP-Dependent Proteases