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Molecular defects of NADH-ubiquinone oxidoreductase (Complex I) in mitochondrial diseases

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Abstract

Defects in Complex I of the mitochondrial respiratory chain have been identified in 38 patients. The clinical and laboratory features are reviewed and the results of recently devised strategies aimed at characterizing the primary molecular and genetic abnormalities are presented. Although not exhaustive, these studies have provided a molecular basis for the contention that defects in Complex I may have their origin in nuclear or in mitochondrial genes.

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References

  • Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperson, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., and Young, I. G. (1981).Nature (London) 290, 457–465.

    Google Scholar 

  • Arts, W. F. M., Scholte, H. R., Bogaad, J. M., Kerrebijm, K. F., and Luyt-Houwen, I. E. M. (1983).Lancet 2, 581–582.

    Google Scholar 

  • Bahr-Lindström, H., Galante, Y. M., Persson, M., and Jörnvall, H. (1983).Eur. J. Biochem. 134, 145–150.

    Google Scholar 

  • Burnett, K. G., and Scheffler, I. E. (1981).J. Cell Biol. 90, 108–115.

    Google Scholar 

  • Cabral, F., and Schatz, G. (1978).J. Biol. Chem. 253, 4396–4401.

    Google Scholar 

  • Capaldi, R. A. (1982).Biochim. Biophys. Acta 694, 291–306.

    Google Scholar 

  • Chen, S., and Guillory, R. J. (1981).J. Biol. Chem. 256, 8318–8323.

    Google Scholar 

  • Chomyn, A., Marriottini, P., Cleeter, M. W. J., Ragan, C. I., Matsumo-Yagi, A., Hatefi, Y., Doolittle, R. F., and Attardi, G. (1985a).Nature (London) 314, 592–597.

    Google Scholar 

  • Chomyn, A., Marriottini, P., Cleeter, M. W. T., Ragan, C. I., Doolittle, R. F., Matsumo-Yagi, A., Hatefi, Y., and Attardi, G. (1985b). InAchievements and Perspectives of Mitochondrial Research (Quagliariello, E., Slater, E. C., Palmieri, F., Saccone, C., and Kroon, A. M., eds.), Vol. II, Elsevier, Amsterdam, pp. 259–275.

    Google Scholar 

  • Clark, J. B., Hayes, D. J., Morgan-Hughes, J. A., and Byrne, E. (1984).J. Inher. Metab. Dis. 7, Suppl. 1, 62–68.

    Google Scholar 

  • Cleeter, M. W. J., Bannister, S. H., and Ragan, C. J. (1985a).Biochem. J. 227, 467–474.

    Google Scholar 

  • Cleeter, M. W. J., Ragan, C. I., Moreadith, R. W., and Lehninger, A. L. (1985b).Biochem. Soc. Trans. 13, 731–732.

    Google Scholar 

  • DiMauro, S., Bonilla, E., Zeviani, M., Nakagawa, M., and DeVivo, D. C. (1985).Ann. Neurol. 17, 521–538.

    Google Scholar 

  • DiMauro, S., Bonilla, E., Zeviani, M., Servidei, S., DeVivo, D. C., and Schon, E. A. (1987).J. Inher. Metab. Dis. 10, Suppl. 1, 113–128.

    Google Scholar 

  • Earley, F. G. P., and Ragan, C. I. (1980).Biochem. J. 191, 429–436.

    Google Scholar 

  • Earley, F. G. P., and Ragan, C. I. (1981).FEBS Lett. 127, 45–47.

    Google Scholar 

  • Earley, F. G. P., and Ragan, C. I. (1984).Biochem. J. 224, 525–534.

    Google Scholar 

  • Frackowiak, R. S. J., Herold, S., Petty, R. K. H., and Morgan-Hughes, J. A. (1988).Brain, in press.

  • Gay, N. J., and Walker, J. E. (1985).EMBO J. 4, 3519–3524.

    Google Scholar 

  • Harding, A. E., Holt, I. J., and Morgan-Hughes, J. A. (1988).J. Med. Genet., in press.

  • Hartl, F-U., Pfanner, N., and Neupert, W. (1986a).Biochem. Soc. Trans. 15, 95–97.

    Google Scholar 

  • Hartl, F-U., Schmidt, B., Wachter, E., Weiss, H., and Neupert, W. (1986b).Cell 47, 939–951.

    Google Scholar 

  • Hatefi, Y. (1985).Annu. Rev. Biochem. 54, 1015–1069.

    Google Scholar 

  • Hatefi, Y., and Stempel, K. E. (1969).J. Biol. Chem. 244, 2350–2357.

    Google Scholar 

  • Hatefi, Y., Haavik, A. G., and Griffiths, D. F. (1962).J. Biol. Chem. 237, 1676–1680.

    Google Scholar 

  • Hatefi, Y., Ragan, C. I., and Galante, Y. M. (1985). InThe Enzymes of Biological Membranes (Martonosi, A. N., ed.), Vol. 4, Plenum Press, New York, pp. 1–70.

    Google Scholar 

  • Hay, R., Bohni, P., and Gasser, S. (1984).Biochim. Biophys. Acta 729, 65–87.

    Google Scholar 

  • Hayes, D. J., Hilton-Hones, D., Arnold, D. L., Galloway, G., Styles, P., Duncan, J., and Radda, G. K. A. (1985).J. Neurol. Sci. 71, 105–118.

    Google Scholar 

  • Heron, C., Smith, S., and Ragan, C. I. (1979).Biochem. J. 181, 435–443.

    Google Scholar 

  • Holt, I. J., Harding, A. E., and Morgan-Hughes, J. A. (1988),Nature (London) 331, 717–719.

    Google Scholar 

  • Hoppel, C. L., Kerr, D. S., Dahms, B., and Roessmann, U. (1987).J. Clin. Invest. 80, 71–77.

    Google Scholar 

  • Kobayashi, M., Morishita, H., Sugiyama, N., Yokochi, K., Nakano, M., Wada, Y., Hotta, Y., Terauchi, A., and Nonada, I. (1987).J. Pediat. 110, 223–227.

    Google Scholar 

  • Kroon, A. M., and Van den Bogert, C. (1987).J. Inher. Metab. Dis. 10, Suppl. 1, 54–61.

    Google Scholar 

  • Kuhn-Nentwig, L., and Kadenbach, B. (1985).Eur. J. Biochem. 149, 147–158.

    Google Scholar 

  • Laemmli, U. K. (1970).Nature (London) 227, 68–685.

    Google Scholar 

  • Land, J. M., Morgan-Hughes, J. A., and Clark, J. B. (1981).J. Neurol. Sci. 50, 1–13.

    Google Scholar 

  • Malczewski, R. M., and Whitfield, C. D. (1984).J. Biol. Chem. 259, 1103–1113.

    Google Scholar 

  • Moreadith, R. W., Batshaw, M. L., Ohnishi, T., Kerr, D., Knox, B., Jackson, D., Hubran, R., Olson, J., Reynafarje, B., and Lehninger, A. L. (1984).J. Clin. Invest. 74, 685–697.

    Google Scholar 

  • Moreadith, R. W., Cleeter, M. W. J., Ragan, I. C., Batshaw, M. L., and Lehninger, A. L. (1987).J. Clin. Invest. 79, 463–467.

    Google Scholar 

  • Morgan-Hughes, J. A. (1982). InSkeletal Muscle Pathology (Mastaglia, F. L., and Walton, J., eds.), Churchill, Livingstone, Edinburgh and London, pp. 309–339.

    Google Scholar 

  • Morgan-Hughes, J. A. (1986a).Trends Neurosci. 9, 15–19.

    Google Scholar 

  • Morgan-Hughes, J. A. (1986b). InMyology (Engel, A. G., and Banker, B. Q., eds.), McGraw-Hill, New York, pp. 1709–1743.

    Google Scholar 

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

    Google Scholar 

  • Morgan-Hughes, J. A., Hayes, D. J., Clark, J. B., Landon, D. N., Swash, M., Stark, R. J., and Rudge, P. (1982).Brain 105, 553–582.

    Google Scholar 

  • Morgan-Hughes, J. A., and Landon, D. N. (1983). InMitochondrial Pathology in Muscle Diseases (Scarlato G., and Cerri, C., eds.), Piccin Medical Books, Padua, Italy, pp. 20–27.

    Google Scholar 

  • Morgan-Hughes, J. A., Hayes, D. J., and Clark, J. B. (1984). InNeuromuscular Diseases (Serratrice, G., Cros, D., Desmuelle, C., Gastaut, J.-L., Pellissier, J.-F., Pouget, J., Schiano, A., eds.) Raven Press, New York, pp. 79–85.

    Google Scholar 

  • Morgan-Hughes, J. A., Hayes, D. J., Cooper, J. M., and Clark, J. B. (1985).Biochem. Soc. Trans. 13, 648–650.

    Google Scholar 

  • Morgan-Hughes, J. A., Cooper, J. M., Schapira, A. H. V., Hayes, D. J., and Clark, J. B. (1987). InThe London Symposia (Ellingson, R. J., Murray, N. M. F., and Halliday, A. M., eds.), Elsevier, Amsterdam, pp. 103–114.

    Google Scholar 

  • Nishizawa, M., Tanaka, K., Shinozawa, K., Kuwabara, T., Atsumi, T., Miyatake, T., and Ohama, F. (1987).J. Neurol. Sci. 78, 189–201.

    Google Scholar 

  • Ohnishi, T., Leigh, J. S., Ragan, C. I., and Racker, E. (1974).Biochem. Biophys. Res. Commun. 56, 775–782.

    Google Scholar 

  • Ohnishi, T., Ragan, C. I., and Hatefi, Y. (1985).J. Biol. Chem. 260, 2782–2788.

    Google Scholar 

  • Parikh, V. S., Morgan, M. M., Scott, R., Clements, L. S., and Butow, R. A. (1987).Science 235, 576–580.

    Google Scholar 

  • Petty, R. K. H., Harding, A. E., and Morgan-Hughes, J. A. (1986).Brain 109, 915–938.

    Google Scholar 

  • Pfanner, N., and Neupert, N. (1985).EMBO J. 4, 2819–2825.

    Google Scholar 

  • Prick, M. J. J., Gabreels, F. J. M., Renier, W. O., Trijbels, J. M. F., Sengers, R. C. A., and Sloof, J. L. (1981).Arch Neurol. 38, 767–772.

    Google Scholar 

  • Przyrembel, H. (1987).J. Inher. Metab. Dis. 10, 129–146.

    Google Scholar 

  • Ragan, C. I. (1985). InCoenzyme Q (Lenaz, G., ed.), Wiley, Chichester, pp. 315–336.

    Google Scholar 

  • Ragan, C. I., and Hinkle, P. C. (1975).J. Biol. Chem. 250, 8472–8476.

    Google Scholar 

  • Ragan, C. I., Galante, Y. M., and Hatefi, Y. (1982a).Biochemistry 21, 2518–2524.

    Google Scholar 

  • Ragan, C. I., Galante, Y. M., Hatefi, Y., and Ohnishi, T. (1982b).Biochemistry 21, 590–594.

    Google Scholar 

  • Robinson, B. H., Ward, J., Goodyer, P., and Baudet, A. (1986).J. Clin. Invest. 77, 1422–1427.

    Google Scholar 

  • Roodhooft, A. M., Van Acker, K. J., Martin, J. J., Ceuterick, C., Scholte, H. R., and Luyt-Houwen, I. E. M. (1986).Neuropediatrics 17, 221–226.

    Google Scholar 

  • Rosing, H. S., Hopkins, L. C., Wallace, D. C., Epstein, C. M., and Weidenheim, K. (1985).Ann. Neurol. 17, 228–237.

    Google Scholar 

  • Schapira, A. H. V., Cooper, J. M., Morgan-Hughes, J. A., and Clark, J. B. (1986).Muscle Nerve 9 (5S), 183.

    Google Scholar 

  • Schapira, A. H. V., Cooper, J. M., Morgan-Hughes, J. A., and Landon, D. N. (1987).J. Neuropathol. Appl. Neurobiol. (abstr.),13, 497.

    Google Scholar 

  • Schapira, A. H. V., Cooper, J. M., Morgan-Hughes, J. A., Patel, S. D., Cleeter, M. J. W., Ragan, C. I., and Clark, J. B. (1988),The Lancet,I, 500–503.

    Google Scholar 

  • Schatz, G., and Butow, R. A. (1983).Cell 32, 316–318.

    Google Scholar 

  • Schleyer, M., and Neupert, W. (1985).Cell 43, 339–350.

    Google Scholar 

  • Scholte, H. R., Busch, H. F. M., Beekman, R. P. M., Berden, J. A., Duran, M., Luyt-Houwen, I. E. M., Przyrembel, H., Roth, B., and De Vries, S. (1983). InMitochondrial Pathology in Muscle Diseases (Scarlato, G., and Cerric, C. eds.), Piccin Medical Books, Padua, Italy, pp. 217–228.

    Google Scholar 

  • Senior, B., and Jungas, R. L. (1974).Pediat. Res. 8, 483a.

  • Sherratt, H. S. A., Cartlidge, N. E. F., Johnson, M. A., and Turnbull, D. M. (1984).J. Inher. Metab. Dis. 7, Suppl. 2, 107–108.

    Google Scholar 

  • Smith, S., and Ragan, C. I. (1980).Biochem. J. 185, 315–326.

    Google Scholar 

  • Tanaka, N., Nishikimi, M., Suzuki, H., Ozawa, T., Nishizawa, M., Tanaka, K., and Miyatake, T. (1986).Biochem. Biophys. Res. Commun. 140, 88–93.

    Google Scholar 

  • Towbin, H., Staehelin, T., and Gordon, J. (1979).Proc. Natl. Acad. Sci. USA 76, 4350–4354.

    Google Scholar 

  • Van Erwen, P. M. M., Gabreels, F. J. M., Ruitenbeek, W., Renler, W. O., and Fischer, J. C. (1987).Arch Neurol. 44, 775–778.

    Google Scholar 

  • Walker, J. E., Cozens, A. L., Dyer, M. R., Fearnley, I. M., Powell, S. J., and Runswick, M. J. (1987).Chem. Scr. B 27, 97–105.

    Google Scholar 

  • Wiles, C. M., Morgan-Hughes, J. A., Rose, P. E., and Weston, M. J. (1986).Hosp. Update 12, 31–42.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Neurology, Queen Square, WC1N 3BG, London

    John A. Morgan-Hughes, Anthony H. V. Schapira & J. Mark Cooper

  2. Department of Biochemistry, St Bartholomew's Hospital Medical School, Charterhouse Square, EC1M 6BQ, London

    J. Mark Cooper & John B. Clark

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  1. John A. Morgan-Hughes
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  2. Anthony H. V. Schapira
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Morgan-Hughes, J.A., Schapira, A.H.V., Cooper, J.M. et al. Molecular defects of NADH-ubiquinone oxidoreductase (Complex I) in mitochondrial diseases. J Bioenerg Biomembr 20, 365–382 (1988). https://doi.org/10.1007/BF00769638

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