Advertisement

Coenzyme Q10 Deficiencies in Neuromuscular Diseases

  • Rafael Artuch
  • Leonardo Salviati
  • Sandra Jackson
  • Michio Hirano
  • Plácido Navas
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 652)

Abstract

Coenzyme Q (CoQ) is an essential component of the respiratory chain but also participates in other mitochondrial functions such as regulation of the transition pore and uncoupling proteins. Furthermore, this compound is a specific substrate for enzymes of the fatty acids β–oxidation pathway and pyrimidine nucleotide biosynthesis. Furthermore, CoQ is an antioxidant that acts in all cellular membranes and lipoproteins. A complex of at least ten nuclear (COQ) genes encoded proteins synthesizes CoQ but its regulation is unknown. Since 1989, a growing number of patients with multisystemic mitochondrial disorders and neuromuscular disorders showing deficiencies of CoQ have been identified. CoQ deficiency caused by mutation(s) in any of the COQ genes is designated primary deficiency. Other patients have displayed other genetic defects independent on the CoQ biosynthesis pathway, and are considered to have secondary deficiencies. This review updates the clinical and molecular aspects of both types of CoQ deficiencies and proposes new approaches to understanding their molecular bases.

Keywords:

Mitochondria Coenzyme Q deficiency Neuromuscular diseases 

Notes

Acknowledgements

This work has been partially supported by the European Union contract LSHB-CT-2004-005151 and the NIH grant 1R01HD057543-01.

References

  1. 1.
    Aeby, A., Sznajer, Y., Cave, H., Rebuffat, E., Van Coster, R., Rigal, O., and Van Bogaert, P. J. 2007, Inherit. Metab. Dis. 30, 827.Google Scholar
  2. 2.
    Artuch, R., Brea-Calvo, G., Briones, P., Aracil, A., Galván, M., Espinós, C., Corral, J., Volponi, V., Ribes, A., Andreu, A.L., Palau, F., Sánchez-Alcázar, J.A., Navas, P., and Pineda, M. 2006, J. Neurol. Sci. 246, 153.CrossRefPubMedGoogle Scholar
  3. 3.
    Artuch, R., Briones, P., Aracil, A., Ribes, A., Pineda, J., Galván, M., Sánchez-Alcázar, J.A., Brea, G., Navas, P., and Pineda, M. 2004, J. Inherit. Metab. Dis., 27 (Suppl 1), 118.Google Scholar
  4. 4.
    Asencio, C. Rodríguez-Aguilera, J.C., Johnson, T.E., Cabello, J., Schnabel, R., and Navas, P. 2009, Mech Ageing Dev. 130:145.Google Scholar
  5. 5.
    Asencio, C., Rodriguez-Aguilera, J.C., Ruiz-Ferrer, M., Vela, J., and Navas, P. 2003. FASEB J, 17, 1135.PubMedGoogle Scholar
  6. 6.
    Ashby, M.N., Kutsunai, S.Y., Ackerman, S., Tzagoloff, A., and Edwards, P.A., 1992. J. Biol. Chem. 267, 4128.PubMedGoogle Scholar
  7. 7.
    Baba, S.W., Belogrudov, G.I., Lee, J.C., Lee, P.T., Strahan, J., Shepherd, J.N., and Clarke, C.F. 2004, J. Biol. Chem. 279, 10052.CrossRefPubMedGoogle Scholar
  8. 8.
    Barros, M.H., Johnson, A., Gin, P., Marbois, B.N., Clarke, C.F., and Tzagoloff, A. 2005, J. Biol. Chem. 280, 42627.CrossRefPubMedGoogle Scholar
  9. 9.
    Belogrudov, G.I., Lee, P.T., Jonassen, T., Hsu, A.Y., Gin, P., and Clarke, C.F. 2001, Arch. Biochim. Biophys. 392, 48.CrossRefGoogle Scholar
  10. 10.
    Boitier, E., Degoul, F., Desguerre, I., Charpentier, C., Francois, D., Ponsot, G., Diry, M., Rustin, P., Marsac, C., and Desguerre, I. 1998, J. Neurol. Sci., 156, 41.CrossRefPubMedGoogle Scholar
  11. 11.
    Casarin, A., Jimenez-Ortega, J.C., Trevisson, E., Pertegato, V., Doimo, M., Ferrero-Gomez, M.L., Abbadi, S., Artuch, R., Quinzii, C., Hirano, M., Basso, G., Santos-Ocaña, C., Navas, P., and Salviati, L. 2008, Biochem. Biophys. Res. Commun. 372, 35.CrossRefPubMedGoogle Scholar
  12. 12.
    Cordero, M.D., Moreno-Fernández, A.M., de Miguel, M., Bonal, P., Campa, F., Jiménez-Jiménez, L.M., Ruiz-Losada, A., Sánchez-Domínguez, B., Sánchez-Alcázar JA, Salviati, L., and Navas P. 2009, Clin. Biochem. 42:732.Google Scholar
  13. 13.
    Crane, F.L., Hatefi, Y., Lester, R.L., and Widmer, C. 1957, Biochim. Biophys. Acta. 25, 220.CrossRefPubMedGoogle Scholar
  14. 14.
    Cui, T.-Z., and Kawamukai, M. 2008, FEBS J. doi:10.111/j.1742-4658.2008.06821.x.Google Scholar
  15. 15.
    De Cabo R., Burgess, J.R., and Navas, P. 2006, J. Bioenerg. Biomembr. 38, 309.CrossRefPubMedGoogle Scholar
  16. 16.
    Do, T.Q., Hsu, A.Y., Jonassen, T., Lee, P.T., and Clarke, C.F. 2001, J. Biol. Chem. 276, 18161.CrossRefPubMedGoogle Scholar
  17. 17.
    Echtay, K.S., Bienengraeber, M., and Klingenberg, M., 2001, Biochemistry 40, 5243.CrossRefPubMedGoogle Scholar
  18. 18.
    Fischer, J.C., Ruitenbeek, W., Gabreels, F.J., Janssen, A.J., Renier, W.O., Sengers, R.C., Stadhouders, A.M., ter Laak, H.J., Trijbels, J.M., and Veerkamp, J.H. 1986, Eur. J. Pediatr., 144, 441.CrossRefPubMedGoogle Scholar
  19. 19.
    Fontaine, E., Ichas, F., and Bernardi, P. 1998, J. Biol. Chem. 273, 25734.CrossRefPubMedGoogle Scholar
  20. 20.
    Forsgren, M., Attersand, A., Lake, S., Grunler, J., Swiezewska, E., Dallner, G., and Climent, I. 2004, Biochem. J. 382, 519.CrossRefPubMedGoogle Scholar
  21. 21.
    Gempel, K., Topaloglu, H., Talim, B., Schneiderat, P., Schoser, B.G., Hans, V.H., Palmafy, B., Kale, G., Tokatli, A., Quinzii, C., Hirano, M., Naini, A., DiMauro, S., Prokisch, H., Lochmuller, H., and Horvath, R. 2007, Brain 130, 2037.CrossRefPubMedGoogle Scholar
  22. 22.
    Gin, P., Hsu, A.Y., Rothman, S.C., Jonassen, T., Lee, P.T., Tzagoloff, A., and Clarke, C.F. 2003, J. Biol. Chem. 278, 25308.CrossRefPubMedGoogle Scholar
  23. 23.
    Gironi, M., Lamperti, C., Nemni, R., Moggio, M., Comi, G., Guerini, F.R., Ferrante, P., Canal, N., Naini, A., Bresolin, N. and DiMauro, S. 2004, Neurology, 62, 818.PubMedGoogle Scholar
  24. 24.
    Hsu, A.Y., Do, T.Q., Lee, P.T., and Clarke, C.F. 2000, Biochim. Biophys. Acta 1484, 287.PubMedGoogle Scholar
  25. 25.
    Jonassen, T., Proft, M., Randez-Gil, F., Schultz, J.R., Marbois, B.N., Entian, K.D., and Clarke, C.F., 1998, J. Biol. Chem. 273, 3351.CrossRefPubMedGoogle Scholar
  26. 26.
    Kagan, V.E., Arroyo, A., Tyurin, V.A., Tyurina, Y.Y., Villalba, J.M., and Navas, P. 1998, FEBS Lett. 428, 43.CrossRefPubMedGoogle Scholar
  27. 27.
    Lagier-Tourenne, C., Tazir, M., López, L.C., Quinzii, C.M., Assoum, M., Drouot, N., Busso, C., Makri, S., Ali-Pacha, L., Benhassine, T., Anheim, M., Lynch, D.R., Thibault, C., Plewniak, F., Bianchetti, L., Tranchant, C., Poch, O., DiMauro, S., Mandel, J.L., Barros, M.H., Hirano, M., and Koenig, M. 2008, Am. J. Hum. Genet. 82, 661.CrossRefPubMedGoogle Scholar
  28. 28.
    Lamperti, C., Naini, A., Hirano, M., De Vivo, D.C., Bertini, E., Servidei, S., Valeriani, M., Lynch, D., Banwell, B., Berg, M., Dubrovsky, T., Chiriboga, C., Angelini, C., Pegoraro, E., and DiMauro, S. 2003, Neurology, 60, 1206.PubMedGoogle Scholar
  29. 29.
    Le Ber, I., Dubourg, O., Benoist, J.F., Jardel, C., Mochel, F., Koenig, M., Brice, M., Lombes, A., and Durr, A. 2007, Neurology, 68, 295.CrossRefPubMedGoogle Scholar
  30. 30.
    Leonard, C.J., Aravind, L., and Koonin, E.V. 1998, Genome Res 8, 1038.PubMedGoogle Scholar
  31. 31.
    Leshinsky-Silver, E., Levine, A., Nissenkorn, A., Barash, V., Perach, M., Buzhaker, E., Shahmurov, M., Polak-Charcon, S., Lev, D., and Lerman-Sagie, T. 2003, Mol. Gen. Metab., 79, 288.CrossRefGoogle Scholar
  32. 32.
    Lopez, L.C., Schuelke, M., Quinzii, C.M., Kanki, T., Rodenburg, R.J., Naini, A., Dimauro, S., and Hirano, M. 2006, Am J Hum Genet 79, 1125.CrossRefPubMedGoogle Scholar
  33. 33.
    López-Martín, J.M., Salviati, L., DiMauro, S., Hirano, M., Rodriguez-Hernandez, A., Cordero, M., Sanchez Alcazar, J.A., Santos-Ocaña, C. and Navas, P. 2007, Hum. Mol. Genet. 16, 1091.CrossRefPubMedGoogle Scholar
  34. 34.
    Mollet, J., Delahodde, A., Serre, V., Chretien, D., Schlemmer, D., Lombes, A., Boddaert, N., Desguerre, I., de Lonlay, P., de Baulny, H.O., Munnich, A., and Rötig, A. 2008, Am J Hum Genet. 82, 623.CrossRefPubMedGoogle Scholar
  35. 35.
    Mollet, J., Giurgea, I., Schlemmer, D., Dallner, G., Chretien, D., Delahodde, A., Bacq, D., de Lonlay, P., Munnich, A., and Rotig, A. 2007, J Clin Invest 117, 765.CrossRefPubMedGoogle Scholar
  36. 36.
    Montero, R., Sáchez-Alcázar, J.A., Briones, P., Rodríguez-Hernández, M.A., Cordero, M.D., Trevisson, E., Salviati, L., Pineda, M., Garcia-Cazorla, A., Navas, P., and Artuch, R. 2008, Clin Biochem. 41, 697.CrossRefPubMedGoogle Scholar
  37. 37.
    Montero, R., S´anchez-Alc´azar, J.A., Briones, P., Navarro-Sastre, A., Gallardo, E., Bornstein, B., Herrero-Martín, D., Rivera, H., Martin, M.A., Marti, R., García-Cazorla, A., Montoya, J., Navas, P., and Artuch, R. 2009, Clin Biochem. 42:742.Google Scholar
  38. 38.
    Montini, G., Malaventura, C., and Salviati, L. 2008, N Engl J Med. 358, 2849.CrossRefPubMedGoogle Scholar
  39. 39.
    Musumeci, O., Naini, A., Slonim, A.E., Skavin, N., Hadjigeorgiou, G.L., Krawiecki, N., Weissman, B.M., Tsao, C.Y., Mendell, J.R., Shanske, S., De Vivo, D.C., Hirano, M., and DiMauro, S. 2001, Neurology, 56, 849.PubMedGoogle Scholar
  40. 40.
    Navas, P., Fernández-Ayala, D.M., Martín, S.F., López-Lluch, G., De Cabo, R., Rodríguez-Aguilera, J.C., and Villalba, J.M. 2002, Free Radic. Res. 36, 369.CrossRefPubMedGoogle Scholar
  41. 41.
    Ogasahara, S., Engel, A.G., Frens, D., and Mack, D. 1989, Proc. Natl. Acad. Sci. USA, 86, 2379.CrossRefPubMedGoogle Scholar
  42. 42.
    Okada, K., Minehira, M., Zhu, X., Suzuki, K., Nakagawa, T., Matsuda, H., and Kawamukai, M., 1997, J. Bacteriol. 179, 3058.PubMedGoogle Scholar
  43. 43.
    Padilla, S., Santos-Ocaña, J.C., Jiménez-Hidalgo, M., López-Martín, J.M., Martín-Montalvo, A., and Navas, P. 2008, Cell. Mol. Life Sci. doi: 10.1007/s00018-008-8547-7.Google Scholar
  44. 44.
    Poon, W.W., Barkovich, R.J., Hsu, A.Y., Frankel, A., Lee, P.T., Shepherd, J.N., Myles, D.C., and Clarke, C.F. 1999, J. Biol. Chem. 274, 21665.CrossRefPubMedGoogle Scholar
  45. 45.
    Quinzii, C.M., DiMauro, S., and Hirano, M. 2007, Neurochem. Res. 32, 723.CrossRefPubMedGoogle Scholar
  46. 46.
    Quinzii, C.M., Kattah, A.G., Naini, A., Akman, H.O., Mootha, V.K., DiMauro, S., and Hirano, M. 2005, Neurology 64, 539.PubMedGoogle Scholar
  47. 47.
    Quinzii, C., Naini, A., Salviati, L., Trevisson, E., Navas, P., DiMauro, S., and Hirano, M. 2006, Am J Hum Genet 78, 345.CrossRefPubMedGoogle Scholar
  48. 48.
    Quinzii, C., López, L.C., Von-Moltke, J., Naini, A., Krishna, S., Schuelke, M., Salviati, L., Navas, P. DiMauro, S., and Hirano, M. 2008, FASEB J 22, 1874.CrossRefPubMedGoogle Scholar
  49. 49.
    Rahman, S., Hargreaves, I., Clayton, P., and Heales, S. 2001, J. Pediatr., 139, 456.CrossRefPubMedGoogle Scholar
  50. 50.
    Rötig, A., Appelkvist, E.L., Geromel, V., Chretien, D., Kadhom, N., Edery, P., Lebideau, M., Dallner, G., Munnich, A., Ernster, L., and Rustin, P. 2000, Lancet, 356, 391.CrossRefPubMedGoogle Scholar
  51. 51.
    Saiki, R., Lunceford, A.L., Shi, Y., Marbois, B., King, R., Pachuski, J., Kawamukai, M., Gasser, D.L., and Clarke. C,F. 2008, Am. J. Physiol. Renal. Physiol. 295, F1535.CrossRefPubMedGoogle Scholar
  52. 52.
    Salviati, L., Sacconi, S., Murer, L., Zacchello, G., Franceschini; L., Laverda, A.M., Basso, G., Quinzii; C., Angelini, C., Hirano, M., Naini, A. B., Navas, P., DiMauro, S., and Montini, G. 2005, Neurology 65, 606.CrossRefPubMedGoogle Scholar
  53. 53.
    Santos-Ocaña, C., Do, T.Q., Padilla, S., Navas, P., and Clarke, C.F, 2002, J. Biol. Chem. 277, 10973.CrossRefPubMedGoogle Scholar
  54. 54.
    Sobreira, C., Hirano, M., Shanske, S., Keller, R.K., Haller, R.G., Davidson, E., Santorelli, F.M., Miranda, A.F., Bonilla, E., Mojon, D.S., Barreira, A.A., King, M.P., and DiMauro, S. 1997, Neurology, 48, 1238.PubMedGoogle Scholar
  55. 55.
    Stenmark, P., Grunler, J., Mattsson, J., Sindelar, P.J., Nordlund, P., and Berthold, D.A., 2001, J. Biol. Chem. 276, 33297.CrossRefPubMedGoogle Scholar
  56. 56.
    Tran, U.C., and Clarke, C.F. 2007, Mitochondrion, 7 Suppl, S62.CrossRefPubMedGoogle Scholar
  57. 57.
    Turunen, M., Olsson, J., and Dallner, G. 2004, Biochim. Biophys. Acta 1660, 171.CrossRefPubMedGoogle Scholar
  58. 58.
    Turunen, M., Swiezewska, E., Chojnacki, T., Sindelar, P., and Dallner, G. 2002, Free Rad. Res., 36, 437.CrossRefGoogle Scholar
  59. 59.
    Vajo, Z., King, L.M., Jonassen, T., Wilkin, D.J., Ho, N., Munnich, A., Clarke, C.F., and Francomano, C.A., 1999, Mamm. Genome 10, 1000.CrossRefPubMedGoogle Scholar
  60. 60.
    Van Maldergem, L., Trijbels, F., DiMauro, S., Sindelar, P.J., Musumeci, O., Janssen, A., Delberghe, X., Martin, J.J., and Gillerot, Y. 2002, Ann. Neurol., 52, 750.CrossRefPubMedGoogle Scholar
  61. 61.
    Villalba, J.M., Navarro, F., Córdoba, F., Serrano, A., Arroyo, A., Crane, F.L., and Navas, P. 1995, Proc. Natl. Acad. Sci. USA 92, 4887.CrossRefPubMedGoogle Scholar
  62. 62.
    Zierz, S., Jahns, G., and Jerusalem, F. 1989, J. Neurol., 236, 97.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Rafael Artuch
    • 1
  • Leonardo Salviati
    • 2
  • Sandra Jackson
    • 3
  • Michio Hirano
    • 4
  • Plácido Navas
    • 5
  1. 1.Biochemistry DepartmentHospital Sant Joan de Déu, Barcelona; CIBER de Enfermedades Raras(CIBERER), ISCIIBarcelonaSpain
  2. 2.Clinical Genetics Unit, Department of PediatricsUniversity of PadovaPadovaItaly
  3. 3.Department of NeurologyTechnical UniversityDresdenGermany
  4. 4.Department of NeurologyColumbia University Medical CenterNew YorkUSA
  5. 5.Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC and CIBER de Enfermedades Raras (CIBERER), ISCIIISevillaSpain

Personalised recommendations