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Gene Review

SCO2  -  SCO2 cytochrome c oxidase assembly protein

Homo sapiens

Synonyms: CEMCOX1, MYP6, Protein SCO2 homolog, mitochondrial, SCO1L
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Disease relevance of SCO2


High impact information on SCO2

  • In the January 3 issue of Cell Metabolism, report that the mitochondrial metallochaperones Sco1 and Sco2, essential for cytochrome c oxidase assembly, are also responsible for maintenance of cell copper homeostasis, thus showing a new function of mitochondria [5].
  • COX activity in patient myoblasts was completely rescued by transduction with a retroviral vector expressing the human SCO2 coding sequence, and more interestingly by addition of copper-histidine (300 microM) to the culture medium [6].
  • Patient fibroblasts showed increased (64)Cu uptake but normal retention values and, consistent with this, the copper concentration was four times higher in Sco2-deficient myoblasts than in controls [6].
  • To investigate the molecular basis of pathogenesis of Sco2 defects in humans we performed genetic and biochemical studies on tissues, myoblasts and fibroblasts from affected patients, as well as on a recombinant human C-terminal Sco2 segment (22 kDa), bearing the putative CxxxC metal-binding motif [6].
  • Immunohistochemical studies suggested that SURF-1 mutations result in similarly reduced levels of mitochondrial-encoded and nuclear-encoded COX subunits, whereas SCO2 mutations affected mitochondrial-encoded subunits to a greater degree [7].

Chemical compound and disease context of SCO2

  • The central chemosensitivity (SCO2), defined as the ratio between change in ventilation (delta V) and delta PETCO2, was assessed either by transient inhalation of gas mixtures containing 5 to 8% CO2 in pure O2 ("varying transients") or by progressive hypercapnia (rebreathing in pure O2) [8].
  • A greater understanding of the pathophysiology of a number of nuclear genetic mitochondrial disorders suggests new avenues for treatment (such as copper-histidine in children with SCO2 gene mutations, and strategies modifying intra-mitochondrial nucleoside pools in the various disorders of mtDNA maintenance) [9].

Biological context of SCO2

  • Overexpression of either wild-type SCO protein in the reciprocal patient background resulted in a dominant-negative phenotype, suggesting a physical interaction between SCO1 and SCO2 [10].
  • Mutations in a mitochondrial copper-binding protein (SCO2) gene were found in nine children with encephalomyopathy and/or cardiomyopathy; all of them were homozygotes or heterozygotes for 1541G>A mutation [11].
  • The Human Cytochrome c Oxidase Assembly Factors SCO1 and SCO2 Have Regulatory Roles in the Maintenance of Cellular Copper Homeostasis [12].
  • At least three proteins, COX17p, SCO1p, and its homologue SCO2p are thought to be involved in mitochondrial copper transport to cytochrome-c-oxidase (COX), the terminal enzyme of the respiratory chain [2].
  • All patients with SCO2 mutations were compound heterozygotes for nonsense or missense mutations [7].

Anatomical context of SCO2

  • Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations [13].
  • Our data demonstrate that the COX deficiency observed in fibroblasts, myoblasts and myotubes from patients with SCO2 mutations can be restored to almost normal levels by the addition of CuCl(2) to the growth medium [13].
  • These data indicate that S225F and E140K mutations found in the SCO2 gene derived from patients alter the physical conformational state of encoded hSco2p that may disturb the normal copper transport pathway in mitochondria [14].
  • We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines [15].
  • SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell [15].

Associations of SCO2 with chemical compounds

  • When these SCO2 structures were studied they were found to lead to deep minima, making CO2 release much more difficult [16].
  • In this pathway a water molecule is inserted in between molybdenum and the SCO2 group [16].
  • By decreasing the GHSV and increasing the reaction temperature AC becomes a specific catalyst for the total toluene oxidation (SCO2 = 100%), but in less favorable conditions CO appears as reaction product and toluene-derivative compounds are retained inside the pores [17].

Regulatory relationships of SCO2

  • In addition to its role as the central regulator of the cellular stress response, p53 can regulate aerobic respiration via the novel transcriptional target SCO2, a critical regulator of the cytochrome c oxidase complex (Matoba et al., 2006) [18].

Other interactions of SCO2

  • Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase [10].
  • In addition, biochemical and morphological studies showed that the COX deficiency was more severe in patients with SCO2 mutations [7].
  • Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells [15].
  • The human Sco2 protein is a cytochrome c oxidase assembly protein that participates in mitochondrial copper pathway, acting downstream of Cox17 protein [14].

Analytical, diagnostic and therapeutic context of SCO2

  • CONCLUSION: The SCO2 mutations should be considered in the differential diagnosis of children with spinal muscular atrophy without mutations in the SMN gene [19].
  • Cerebrovascular hemoglobin oxygen saturation (SCO2), an index of brain oxygenation, was monitored intraoperatively by near-infrared spectroscopy [20].
  • The results demonstrated that our near-infrared TRS method can be used to monitor mu'(s), SCO2, CBV, and DPF in the neonatal brain at the bedside in an intensive care unit [21].
  • RESULTS: Relative to preoperative levels, the age groups experienced similar changes in SCO2 during surgery: SCO2 increased 30 +/- 4% during deep hypothermic CPB, it decreased 62 +/- 5% by the end of arrest, and it increased 20 +/- 5% during CPB recirculation (all P < 0.001); after rewarming and removal of CPB, SCO2 returned to preoperative levels [20].
  • The arterial and venous contribution to cerebral oximetry was 16 +/- 21% and 84 +/- 21%, respectively (where Sco2 = alpha Sao2 + beta Sjo2 with alpha and beta being arterial and venous contributions) [22].


  1. Mutation screening in patients with isolated cytochrome c oxidase deficiency. Sacconi, S., Salviati, L., Sue, C.M., Shanske, S., Davidson, M.M., Bonilla, E., Naini, A.B., De Vivo, D.C., DiMauro, S. Pediatr. Res. (2003) [Pubmed]
  2. Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency. Horvath, R., Lochmüller, H., Stucka, R., Yao, J., Shoubridge, E.A., Kim, S.H., Gerbitz, K.D., Jaksch, M. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  3. Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type I phenotype. Tarnopolsky, M.A., Bourgeois, J.M., Fu, M.H., Kataeva, G., Shah, J., Simon, D.K., Mahoney, D., Johns, D., MacKay, N., Robinson, B.H. Am. J. Med. Genet. A (2004) [Pubmed]
  4. Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality. Tay, S.K., Shanske, S., Kaplan, P., DiMauro, S. Arch. Neurol. (2004) [Pubmed]
  5. The scoop on sco. Brière, J.J., Tzagoloff, A. Mol. Cell (2007) [Pubmed]
  6. Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts. Jaksch, M., Paret, C., Stucka, R., Horn, N., Müller-Höcker, J., Horvath, R., Trepesch, N., Stecker, G., Freisinger, P., Thirion, C., Müller, J., Lunkwitz, R., Rödel, G., Shoubridge, E.A., Lochmüller, H. Hum. Mol. Genet. (2001) [Pubmed]
  7. Differential features of patients with mutations in two COX assembly genes, SURF-1 and SCO2. Sue, C.M., Karadimas, C., Checcarelli, N., Tanji, K., Papadopoulou, L.C., Pallotti, F., Guo, F.L., Shanske, S., Hirano, M., De Vivo, D.C., Van Coster, R., Kaplan, P., Bonilla, E., DiMauro, S. Ann. Neurol. (2000) [Pubmed]
  8. Assessment of the central chemosensitivity in man under transient or progressive hypercapnia. Jammes, Y., Fornaris, M., Vanuxem, D., Grimaud, C. Arch. Int. Physiol. Biochim. (1980) [Pubmed]
  9. New approaches to the treatment of mitochondrial disorders. Chinnery, P.F. Reprod. Biomed. Online (2004) [Pubmed]
  10. Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase. Leary, S.C., Kaufman, B.A., Pellecchia, G., Guercin, G.H., Mattman, A., Jaksch, M., Shoubridge, E.A. Hum. Mol. Genet. (2004) [Pubmed]
  11. Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. Böhm, M., Pronicka, E., Karczmarewicz, E., Pronicki, M., Piekutowska-Abramczuk, D., Sykut-Cegielska, J., Mierzewska, H., Hansikova, H., Vesela, K., Tesarova, M., Houstkova, H., Houstek, J., Zeman, J. Pediatr. Res. (2006) [Pubmed]
  12. The Human Cytochrome c Oxidase Assembly Factors SCO1 and SCO2 Have Regulatory Roles in the Maintenance of Cellular Copper Homeostasis. Leary, S.C., Cobine, P.A., Kaufman, B.A., Guercin, G.H., Mattman, A., Palaty, J., Lockitch, G., Winge, D.R., Rustin, P., Horvath, R., Shoubridge, E.A. Cell metabolism (2007) [Pubmed]
  13. Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations. Salviati, L., Hernandez-Rosa, E., Walker, W.F., Sacconi, S., DiMauro, S., Schon, E.A., Davidson, M.M. Biochem. J. (2002) [Pubmed]
  14. Human recombinant mutated forms of the mitochondrial COX assembly Sco2 protein differ from wild-type in physical state and copper binding capacity. Foltopoulou, P.F., Zachariadis, G.A., Politou, A.S., Tsiftsoglou, A.S., Papadopoulou, L.C. Mol. Genet. Metab. (2004) [Pubmed]
  15. p53 regulates mitochondrial respiration. Matoba, S., Kang, J.G., Patino, W.D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P.J., Bunz, F., Hwang, P.M. Science (2006) [Pubmed]
  16. Quantum chemical modeling of CO oxidation by the active site of molybdenum CO dehydrogenase. Siegbahn, P.E., Shestakov, A.F. Journal of computational chemistry. (2005) [Pubmed]
  17. Activated carbon and tungsten oxide supported on activated carbon catalysts for toluene catalytic combustion. Alvarez-Merino, M.A., Ribeiro, M.F., Silva, J.M., Carrasco-Marín, F., Maldonado-Hódar, F.J. Environ. Sci. Technol. (2004) [Pubmed]
  18. p53 aerobics: the major tumor suppressor fuels your workout. Kruse, J.P., Gu, W. Cell metabolism. (2006) [Pubmed]
  19. Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease. Salviati, L., Sacconi, S., Rasalan, M.M., Kronn, D.F., Braun, A., Canoll, P., Davidson, M., Shanske, S., Bonilla, E., Hays, A.P., Schon, E.A., DiMauro, S. Arch. Neurol. (2002) [Pubmed]
  20. Cerebral oxygenation during pediatric cardiac surgery using deep hypothermic circulatory arrest. Kurth, C.D., Steven, J.M., Nicolson, S.C. Anesthesiology (1995) [Pubmed]
  21. Developmental changes of optical properties in neonates determined by near-infrared time-resolved spectroscopy. Ijichi, S., Kusaka, T., Isobe, K., Okubo, K., Kawada, K., Namba, M., Okada, H., Nishida, T., Imai, T., Itoh, S. Pediatr. Res. (2005) [Pubmed]
  22. Arterial and venous contributions to near-infrared cerebral oximetry. Watzman, H.M., Kurth, C.D., Montenegro, L.M., Rome, J., Steven, J.M., Nicolson, S.C. Anesthesiology (2000) [Pubmed]
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