Advertisement

Journal of Bioenergetics and Biomembranes

, Volume 38, Issue 5–6, pp 283–291 | Cite as

Cytochrome c oxidase subunit IV is essential for assembly and respiratory function of the enzyme complex

  • Youfen Li
  • Jeong-Soon Park
  • Jian-Hong Deng
  • Yidong Bai
Original Paper

Abstract

Cytochrome c oxidase or complex IV, catalyzes the final step in mitochondrial electron transfer chain, and is regarded as one of the major regulation sites for oxidative phosphorylation. This enzyme is controlled by both nuclear and mitochondrial genomes. Among its 13 subunits, three are encoded by mitochondrial DNA and ten by nuclear DNA. In this work, an RNA interference approach was taken which led to the generation of mouse A9 cell derivatives with suppressed expression of nuclear-encoded subunit IV (COX IV) of this complex. The amounts of this subunit are decrease by 86% to 94% of normal level. A detail biosynthetic and functional analysis of several cell lines with suppressed COX IV expression revealed a loss of assembly of cytochrome c oxidase complex and, correspondingly, a reduction in cytochrome c oxidase-dependent respiration and total respiration. Furthermore, dysfunctional cytochrome c oxidase in the cells leads to a compromised mitochondrial membrane potential, a decreased ATP level, and failure to grow in galactose medium. Interestingly, suppression of COX IV expression also sensitizes the cells to apoptosis. These observations provide the evidence of the essential role of the COX IV subunit for a functional cytochrome c oxidase complex and also demonstrate a tight control of cytochrome c oxidase over oxidative phosphorylation. Finally, our results further shed some insights into the pathogenic mechanism of the diseases caused by dysfunctional cytochrome c oxidase complex.

Keywords

Mitochondria Cytochrome c oxidase complex RNA interference Subunit IV of complex IV Complex IV assembly Mitochondrial respiration Mitochondrial membrane potential ATP synthesis Apoptosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Bibliography

  1. 1.
    Capaldi RA (1990) Annu Rev Biochem 59:569–596CrossRefGoogle Scholar
  2. 2.
    Barrientos A, Barros M H, Valnot I, Rotig A, Rustin P, Tzagoloff A (2002) Gene 286:53–63CrossRefGoogle Scholar
  3. 3.
    Kadenbach B, Huttemann M, Arnold S, Lee I, Bender E (2000) Free Radic Biol Med 29:211–221CrossRefGoogle Scholar
  4. 4.
    Attardi G, Schatz G (1988) Annu Rev Cell Biol 4:289–333CrossRefGoogle Scholar
  5. 5.
    Villani G, Greco M, Papa S, Attardi G (1998) J Biol Chem 273:31829–31836CrossRefGoogle Scholar
  6. 6.
    Shoubridge EA (2001) Am J Med Genet 106:46–52CrossRefGoogle Scholar
  7. 7.
    Littlefield JW (1963) Proc Natl Acad Sci USA 50:568–573CrossRefGoogle Scholar
  8. 8.
    Chomyn A (1996) Methods Enzymol 264:197–211Google Scholar
  9. 9.
    Nijtmans LG, Henderson NS, Holt IJ (2002) Methods 26:327–334CrossRefGoogle Scholar
  10. 10.
    Schagger H (1996) Methods Enzymol 264:555–566Google Scholar
  11. 11.
    Bai Y, Attardi G (1998) Embo J 17:4848–4858CrossRefGoogle Scholar
  12. 12.
    Hofhaus G, Shakeley RM, Attardi G (1996) Methods Enzymol 264:476–483Google Scholar
  13. 13.
    Wong A, Cortopassi, GA (2002) Biochem Biophys Res Commun 298:750–754CrossRefGoogle Scholar
  14. 14.
    Hayashi J, Ohta S, Kikuchi A, Takemitsu M, Goto Y, Nonaka I (1991) Proc Natl Acad Sci USA 88:10614–10618CrossRefGoogle Scholar
  15. 15.
    Schagger H (1995) Methods Enzymol 260:190–202CrossRefGoogle Scholar
  16. 16.
    Bai Y, Hu P, Park JS, Deng JH, Song X, Chomyn A, Yagi T, Attardi G (2004) Ann N Y Acad Sci 1011:272–283CrossRefGoogle Scholar
  17. 17.
    Chen LB (1988) Annu Rev Cell Biol 4:155–181CrossRefGoogle Scholar
  18. 18.
    Robinson BH (1996) Methods Enzymol 264:454–464Google Scholar
  19. 19.
    Kroemer G (2003) Biochem Biophys Res Commun 304:433–435CrossRefGoogle Scholar
  20. 20.
    Polster BM, Fiskum G. (2004) J Neurochem 90:1281–1289CrossRefGoogle Scholar
  21. 21.
    Danielson SR, Wong A, Carelli V, Martinuzzi A, Schapira AH, Cortopassi GA (2002) J Biol Chem 277:5810–5815CrossRefGoogle Scholar
  22. 22.
    Wang X (2001) Genes Dev 15:2922–2933Google Scholar
  23. 23.
    Bruno C, Martinuzzi A, Tang Y, Andreu AL, Pallotti F, Bonilla E, Shanske S, Fu J, Sue CM, Angelini C, DiMauro S, Manfredi G (1999) Am J Hum Genet 65:611–620CrossRefGoogle Scholar
  24. 24.
    Clark KM, Taylor RW, Johnson MA, Chinnery PF, Chrzanowska-Lightowlers ZM, Andrews RM, Nelson IP, Wood NW, Lamont PJ, Hanna MG, Lightowlers RN, Turnbull DM (1999) Am J Hum Genet 64:1330–1339CrossRefGoogle Scholar
  25. 25.
    Rahman S, Taanman JW, Cooper JM, Nelson I, Hargreaves I, Meunier B, Hanna MG, Garcia JJ, Capaldi RA, Lake BD, Leonard JV, Schapira AH (1999) Am J Hum Genet 65:1030–1039CrossRefGoogle Scholar
  26. 26.
    Tiranti V, Corona P, Greco M, Taanman JW, Carrara F, Lamantea E, Nijtmans L, Uziel G, Zeviani M (2000) Hum Mol Genet 9:2733–2742CrossRefGoogle Scholar
  27. 27.
    D'Aurelio M, Pallotti F, Barrientos A, Gajewski CD, Kwong JQ, Bruno C, Beal MF, Manfredi G (2001) J Biol Chem 276:46925–46932CrossRefGoogle Scholar
  28. 28.
    Ludwig B, Bender E, Arnold S, Huttemann M, Lee I, Kadenbach B (2001) Chembiochem 2:392–403CrossRefGoogle Scholar
  29. 29.
    Lenaz G, D'Aurelio M, Merlo Pich M, Genova ML, Ventura B, Bovina C, Formiggini G, Parenti Castelli G (2000) Biochim Biophys Acta 1459:397–404CrossRefGoogle Scholar
  30. 30.
    Ferguson M, Mockett RJ, Shen Y, Orr WC, Sohal RS (2005) Biochem J 390:501–511CrossRefGoogle Scholar
  31. 31.
    Navarro A, Sanchez Del Pino MJ, Gomez C, Peralta JL, Boveris A (2002) Am J Physiol Regul Integr Comp Physiol 282:R985–992Google Scholar
  32. 32.
    Sullivan PG, Brown MR (2005) Prog Neuropsychopharmacol Biol Psychiatry 29:407–410CrossRefGoogle Scholar
  33. 33.
    Nicholls DG (2004) Aging Cell 3:35–40CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Youfen Li
    • 1
  • Jeong-Soon Park
    • 1
  • Jian-Hong Deng
    • 1
  • Yidong Bai
    • 1
  1. 1.Department of Cellular and Structural BiologyUniversity of Texas Health Sciences Center at San AntonioSan AntonioUSA

Personalised recommendations