Cox17p is essential for the assembly of functional cytochrome c oxidase (CCO). Binds and delivers two copper ions to the metallochaperone SCO1 which transports the copper ions to the Cu(A) site on the cytochrome c oxidase subunit II (MT-CO2/COX2) [, ].
This entry represents cytochrome c oxidase assembly factors Sco1 and Sco2 (Synthesis of Cytochrome c Oxidase, factors 1 and 2), mitochondrial inner membrane-tethered metallochaperones that have regulatory roles in the maintenance of cellular copper homeostasis. These proteins are essential for the assembly of the catalytic core of cytochrome c oxidase (COX or complex IV), as well as other roles in copper homeostasis such as mitochondrial redox signalling []. Both Sco1 and Sco2 contain highly conserved CXXXC motifs thought to be required for copper binidng.COX is the terminal enzyme of the energy transducing respiratory chain in eukaryotes and certain prokaryotes. It catalyses the transfer of electrons from cytochrome c to molecular oxygen and pumps protons across the mitochondrial inner membrane to establish a proton gradient for ATP synthesis. It consists of 12-13 protein subunits, with 3 subunits (Cox1-Cox3) forming the enzyme core. COX uses haem and copper as cofactors: Cox1 contains a 1-copper centre (CuB) that interacts with the haem moiety and Cox2 contains a 2-copper centre (CuA). Sco1 and Sco2 act as copper chaperones, transporting copper to the CuA site in Cox2, and are thought to have cooperative functions in COX assembly [, ]. In addition, human Sco2 is also the downstream mediator of the balance between the utilization of respiratory and glycolytic pathways []and both Sco1 and Sco2 may have regulatory roles in regulating cellular copper levels (homeostasis) []. Sco2 may have a copper-level-detection signalling role, acting upstream and in conjunction with Sco1.Defects in Sco1 are a cause of cytochrome c oxidase deficiency (COX deficiency) (OMIM:220110), a clinically heterogeneous disorder with features ranging from isolated myopathy to severe multisystem disease, and onset from infancy to adulthood. Defects in Sco2 are the cause of fatal infantile cardioencephalomyopathy with cytochrome c oxidase deficiency (FIC) (OMIM:604377, OMIM:220110), which is characterised by hypertrophic cardiomyopathy, lactic acidosis, and gliosis.
The SCO (an acronym for Synthesis of Cytochrome c Oxidase) family is involved in biogenesis of respiratory and photosynthetic systems. Members of this family are required for the proper assembly of cytochrome c oxidase (COX). They contain a metal binding motif, typically CXXXC, which is located in a flexible loop. In yeast the SCO1 protein is specifically required for a post-translational step in the accumulation of subunits 1 and 2 of cytochrome c oxidase (COXI and COX-II) []. It is a mitochondrion-associated cytochrome c oxidase assembly factor, and a membrane-anchored protein possessing a soluble domain with a TRX fold []. The SCOP homologue in Bacillus subtilis is also required for the expression of cytochrome c oxidase []. It has been proposed that Sco1 specifically delivers copper to the CuA site, a dinuclear copper centre, of the COX II subunit. More recently, it has been argued that the redox sensitivity of the copper binding properties of Sco1 implies that it participates in signaling events rather than functioning as a chaperone that transfers copper to COX II [, ].The purple nonsulphur photosynthetic eubacterium Rhodobacter capsulatus is a versatile organism that can obtain cellular energy by several means, including the capture of light energy for photosynthesis as well as the use of light-independent respiration, in which molecular oxygen serves as a terminal electron acceptor. The SenC protein is required for optimal cytochrome c oxidase activity in aerobically grown R. capsulatus cells and is involved in the induction of structural polypeptides of the light-harvesting and reaction centre complexes [].Mutations in human Sco1 and Sco2 cause fatal infantile hepatoencephalomyopathy and cardioencephalomyopathy, respectively. Both disorders are associated with severe COX deficiency in affected tissues [].
Bacterial translation elongation factor G (EF-G) catalyses translocation during peptide elongation and mediates ribosomal disassembly during ribosome recycling with the aid of the ribosomal recycling factor (RRF). This entry represents plant plastid EF-G (also known as SCO1), which displays a 59% homology to prokaryotic EF-G proteins. It is a chloroplast-localised elongation factor involved in protein synthesis in plastids. In Arabidopsis, the mutations in sco1 affect thechloroplast mRNA translation that does not only influence chlorophyll accumulation during chloroplast formation in cotyledons, but also other developmental processes such as germination and flowering [].
