Skip to main content
Log in

Human NADH:Ubiquinone Oxidoreductase

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

NADH:ubiquinone oxidoreductase consists of at least 43 proteins; seven are encoded by the mitochondrial genome, while the remainder are encoded by the nuclear genome. A deficient activity of this enzyme complex is frequently observed in the clinical heterogeneous group of mitochondrial disorders, with Leigh (-like) disease as the main contributor. Enzyme complex activity measurement in skeletal muscle is the mainstay of the diagnostic process. Fibroblast studies are a prerequisite whenever prenatal enzyme diagnosis is considered. Mitochondrial DNA mutations are found in approximately 5–10% of all complex I deficiencies. Recently, all structural nuclear complex I genes have been determined at the cDNA level and several at the gDNA level. A comprehensive mutational analysis study of all complex I nuclear genes in a group of 20 patients exhibiting this deficiency revealed mutations in about 40%. Here, we describe the enzymic methods we use and the recent progress made in genomics and cell biology of human complex I.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Attardi, B., Cravioto, B., and Attardi, G. (1969). J. Mol. Biol. 44, 47–70.

    Google Scholar 

  • Chinnery, P. F., and Turnbull, D. M. (1997). J. Neurol. Neurosurg. Psych. 63, 559–563.

    Google Scholar 

  • de Coo, R., Buddiger, P., Smeets, H., Geurts van Kessel, A., Morgan Hughes, J., Weghuis, D. O., Overhauser, J., and van Oost, B. (1995). Genomics 26, 461–466.

    Google Scholar 

  • de Coo, R. F. M., Buddiger, P., Smeets, H. J. M., and van Oost, B. A. (1997). Genomics 45, 434–437.

    Google Scholar 

  • de Coo, R. F. M., Buddiger, P. A. L., Smeets, H. J. M., and van Oost, B. A. (1999). Mammal. Genome 10, 49–53.

    Google Scholar 

  • de Sury, R., Martinez, P., Procaccio, V., Lunardi, J., and Issartel, J. P. (1998). Gene 215, 1–10.

    Google Scholar 

  • Emahazion, T., and Brookes, A. J. (1998). Cytogenet. Cell. Genet. 82, 114–114.

    Google Scholar 

  • Emahazion, T., Beskow, A., Gyllensten, U., and Brookes, A. J. (1998). Cytogenet. Cell. Genet. 82, 115–119.

    Google Scholar 

  • Faivre, L., Cormier-Daire,V., Chretien, D., Christoph Von Kleist-Retzow J., Amiel, J., Dommergues, M., Saudubray, J. M., Dumez, Y., Rotig, A., Rustin, P., and Munnich, A. (2000). Prenatal Diag. 20, 732–737.

    Google Scholar 

  • Fischer, J. C., Ruitenbeek, W., Stadhouders, A. M., Trijbels, J. M., Sengers, R. C., Janssen, A. J., and Veerkamp, J. H. (1985). Clin. Chim. Acta 145 89–99.

    Google Scholar 

  • Hattori, N., Suzuki, H., Wang, Y., Minoshima, S., Shimizu, N., Yoshino, H., Kurashima, R., Tanaka, M., Ozawa, T., and Mizuno, Y. (1995). Biochem. Biophys. Res. Commun. 216, 771–777.

    Google Scholar 

  • Kirby, D. M., Crawford, M., Cleary, M. A., Dahl, H. H., Dennett, X., and Thorburn, D. R. (1999). Neurology 52, 1255–1264.

    Google Scholar 

  • Kirby, D. M., Kahler, S. G., Freckmann, M. L., Reddihough, D., and Thorburn, D. R. (2000). Ann. Neurol. 48, 102–104.

    Google Scholar 

  • Lin, X., Wells, D. E., Kimberling, W. J., and Kumar, S. (1999). Human. Heredity. 49, 75–80.

    Google Scholar 

  • Loeffen, J. L., Triepels, R. H., van den Heuvel, L. P., Schuelke, M., Buskens, C. A., Smeets, R. J., Trijbels, J. M., and Smeitink, J. A. (1998). Biochem. Biophys. Res. Commun. 253, 415–422.

    Google Scholar 

  • Loeffen, J. L., Smeitink, J. A., Trijbels, J. M., Janssen, A. J., Triepels, R. H., Sengers, R. C., and van den Heuvel, L. P. (2000). Human. Mut. 15, 123–134.

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). J. Biol. Chem. 193, 265–275.

    Google Scholar 

  • Morgan-Hughes, J. A., Darveniza, P., Landon, D. N., Land, J. M., and Clark, J. B. (1979). J. Neurol. Sci. 43, 27–46.

    Google Scholar 

  • Papa, S., Sardanelli, A. M., Cocco, T., Speranza, F., Scacco, S. C., and Technikova Dobrova, Z. (1996). FEBS Lett. 379, 299–301.

    Google Scholar 

  • Papa, S., Scacco, S., Sardanelli, A. M., Vergari, R., Papa, F., Budde, S., van den Heuvel, L., and Smeitink, J. (2001). FEBS Lett. 489, 259–262.

    Google Scholar 

  • Pitkanen, S., Feigenbaum, A., Laframboise, R., and Robinson, B. H. (1996). J. Inherit. Metab. Dis. 19, 675–686.

    Google Scholar 

  • Procaccio, V., Mousson, B., Beugnot, R., Duborjal, H., Feillet, F., Putet, G., Pignot-Paintrand, I., Lombes, A., De Coo, R., Smeets, H., Lunardi, J., and Issartel, JP. (1999). J. Clin. Invest. 104, 83–92.

    Google Scholar 

  • Procaccio, V., Lescuyer, P., Bourges, I., Beugnot, R., Duborjal, H., Depetris, D., Mousson, B., Montfort, M. F., Smeets, H., de Coo R., and Issartel, J. P. (2000). Mammal. Genome 11, 808–810.

    Google Scholar 

  • Robinson, B. H. (1993). Biochim. Biophys. Acta 1182, 231–244.

    Google Scholar 

  • Rubio-Gozalbo, M. E., Sengers, R. C., Trijbels, J. M., Doesburg, W. H., Janssen, A. J., Verbeek, A. L., and Smeitink, J. A. (2000). Neuropediatrics 31, 114–121.

    Google Scholar 

  • Schuelke, M., Loeffen, J., Mariman, E., Smeitink, J., and van den Heuvel, L. (1998). Biochem. Biophys. Res. Commun. 245, 599–606.

    Google Scholar 

  • Skehel, J. M., Fearnley, I. M., and Walker, J. E. (1998). FEBS Lett. 438, 301–305.

    Google Scholar 

  • Smeitink, J., and van den Heuvel, L. (1999). Amer. J. Human. Genet. 64, 1505–1510.

    Google Scholar 

  • Smeitink, J. A. M., Loeffen, J. L. C. M., Triepels, R. H., Smeets, R. J. P., Trijbels, J. M. F., and van den Heuvel, L. P. (1998). Human. Mol. Genet. 7, 1573–1579.

    Google Scholar 

  • Srere, P. A. (1969). Methods Enzymol. 13, 3–11.

    Google Scholar 

  • Thorburn, D. R. (2000). Human. Reprod. 15, 57–67.

    Google Scholar 

  • Triepels, R. H., van den Heuvel, L. P., Loeffen, J. L., Buskens, C. A., Smeets, R. J., Rubio Gozalbo, M. E., Budde, S. M., Mariman, E. C., Wijburg, F. A., Barth, P. G., Trijbels, J. M., and Smeitink, J. A. (1999). Ann. Neurol. 45, 787–790.

    Google Scholar 

  • Triepels, R., Smeitink, J., Loeffen, J., Smeets, R., Trijbels, F., and van den Heuvel, L. (2000). Human. Genet. 106, 385–391.

    Google Scholar 

  • Triepels, R. H., Hanson, B. J., van den Heuvel, L. P., Sundell, L., Marusich, M. F., Smeitink, J. A., and Capaldi, R. A. (2001). J. Biol. Chem. 276, 8892–8897.

    Google Scholar 

  • Trijbels, J. M., Sengers, R. C., Ruitenbeek, W., Fischer, J. C., Bakkeren, J. A., and Janssen, A. J. (1988). Eur. J. Pediatr. 148, 92–97.

    Google Scholar 

  • Trijbels, J. M., Scholte, H. R., Ruitenbeek, W., Sengers, R. C., Janssen, A. J., and Busch, H. F. (1993). Eur. J. Pediatr. 152, 178–184.

    Google Scholar 

  • van den Heuvel, L., and Smeitink, J. (2001). BioEssays, in press.

  • van den Heuvel, L., Ruitenbeek, W., Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., and Smeitink, J. (1998). Amer. J. Human. Genet. 62, 262–268.

    Google Scholar 

  • von Kleist-Retzow, J. C., Vial, E., Chantrel-Groussard, K., Rotig, A., Munnich, A., Rustin, P., and Taanman, J. W. (1999). Biochim. Biophys. Acta 1455, 35–44.

    Google Scholar 

  • Walker, J. E. (1992). Quart. Rev. Biophys. 25, 253–324.

    Google Scholar 

  • Zhuchenko, O., Wehnert, M., Bailey, J., Sun, Z. S., and Lee, C. C. (1996). Genomics 37, 281–288.

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smeitink, J., Sengers, R., Trijbels, F. et al. Human NADH:Ubiquinone Oxidoreductase. J Bioenerg Biomembr 33, 259–266 (2001). https://doi.org/10.1023/A:1010743321800

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1010743321800

Navigation