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Structure, Function and Pathology of Complex I

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Mitochondrial Diseases

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Abstract

In eukaryote cells, substrates are terminally oxidized by enzymatic complexes of the respiratory chain located in the inner membrane of mitochondria. Oxidation of NADH or FADH2 by these enzymes is coupled to an ejection of protons into the intermembrane space. The resulting electrochemical gradient drives ATP synthesis which is achieved by re-entry of protons through the ATP synthetase.

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References

  • Albracht SP J, de Jong AM (1997) Bovine-heart NADH: ubiquinone oxidoreductase is a monomer with 8 Fe-S clusters and 2 FMN groups. Biochim Biophys Acta 1140:105–134

    Google Scholar 

  • Ali ST, Duncan AMV, Schappert K, Heng HHQ, Tsui LC, Chow W, Robinson BH (1993) Chromosomal localization of the human gene encoding the 51-kDa subunit of mitochondrial complex I (NDUFV1) to 11ql3. Genomics 18:435–439

    Article  PubMed  CAS  Google Scholar 

  • Baens M, Chaffanet M, Cassiman J-J, van den Berghe H, Marynen P (1993) Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid. Genomics 16:214–218

    Article  PubMed  CAS  Google Scholar 

  • Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, Viegas-Péquignot E, Munnich A, Rötig A (1995) Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 11:144–149

    Article  PubMed  CAS  Google Scholar 

  • Brandt U (1997) Proton translocation by membrane-bound NADH:ubiquinone-oxidoreductase (complex I) through redox-gated ligand conduction. Biochim Biophys Acta 1318:79–91

    Article  PubMed  CAS  Google Scholar 

  • Chevallet M, Dupuis A, Lunardi J, Van Beizen R, Albracht SP J, Issartel JP (1997) The NUOI subunit of the Rhodobacter capsulatus respiratory complex I (equivalent to the bovine TYKY subunit) is required for proper assembly of the membraneous and peripheral arms of the enzyme. Eur J Biochem 250:451–458

    Article  PubMed  CAS  Google Scholar 

  • Chomyn A, Mariottini P, Cleeter MWJ, Ragan CI, Matsuno-Yagi A, Hatefi Y, Doolittle RF, Attardi G (1985) Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase. Nature 314:592–597

    Article  PubMed  CAS  Google Scholar 

  • Darrouzet E, Issartel J-P, Lunardi J, Dupuis A (1998) The 49 kDa subunit of NADH-ubiquinone oxidoreductase (complex I) is involved in the binding of piericidin and rotenone, two quinone-related inhibitors. FEBS Lett 431:34–38

    Article  PubMed  CAS  Google Scholar 

  • De Coo R, Buddiger P, Smeets H, van Kessel AG, Morgan-Hughes J, Wehuis DO, Overhauser J, van Oost B (1995) Molecular cloning and characterization of the active human mitochondrial NADH:ubiquinone oxidoreductase 24 kDa gene (NDUFV2) and its pseudogene. Genomics 26:461–466

    Article  PubMed  Google Scholar 

  • De Coo R, Buddiger P, Smeets H, Van Oost B (1997) Molecular cloning and characterization of the human mitochondrial NADH:oxidoreductase 10 kDa gene (NDUFV3). Genomics 45:434–437

    Article  PubMed  Google Scholar 

  • Degli-Esposti M (1998) Inhibitors of NADH-ubiquinone reductase: an overview. Biochim Biophys Acta 1364:222–235

    Article  PubMed  CAS  Google Scholar 

  • Dunbar DR, Shibasaki Y, Dobbie L, Andersson B, Brookes AJ (1997) In situ hybridization mapping of genomic clones for five human respiratory chain complex I genes. Cytogenet Cell Genet 78:21–24

    Article  PubMed  CAS  Google Scholar 

  • Duncan AMV, Chow W, Robinson BH (1992) Localization of the human 75 kDa I Fe-S protein of NADH-coenzyme Q reductase gene (NDUFS1) to 2q33→q34. Cytogenet Cell Genet 60:212–213

    Article  PubMed  CAS  Google Scholar 

  • Dupuis A (1992) Identification of two genes of Rhodobacter capsulatus coding for proteins homologous to the ND1 and 23 kDa subunits of the mitochondrial complex I. FEBS Lett 30:215–218

    Article  Google Scholar 

  • Dupuis A, Peinnequin A, Chevallet M, Lunardi J, Darrouzet E, Pierrard B, Procaccio V, Issartel JP (1995) Identification of five Rhodobacter capsulatus genes encoding the equivalent of ND subunits of the mitochondrial NADH-ubiquinone oxidoreductase. Gene 167:99–104

    Article  PubMed  CAS  Google Scholar 

  • Earley FG, Patel SD, Ragan CI, Attardi G (1987) Photolabeling of a mitochondrially-encoded subunit of NADH dehydrogenase with [3H]dihydrorotenone. FEBS Lett 219:110–113

    Article  Google Scholar 

  • Frattini A, Faranda S, Bagnasco L, Patrosso C, Nulli P, Zucchi I, Vezzoni P (1997) Identification of a new member (ZNF183) of the Ring finger gene family in Xq24–25. Gene 192:291–298

    Article  PubMed  CAS  Google Scholar 

  • Gu JZ, Lin X, Wells DE (1996) The human B22 subunit of the NADH:ubiquinone oxidoreductase maps to the region of chromosome 8 involved in branchio-oto-renal syndrome. Genomics 35:6–10

    Article  PubMed  CAS  Google Scholar 

  • Guénebaut V, Vincentelli R, Mills D, Weiss H, Leonard KR (1997) Three-dimensional structure of NADH-dehydrogenase from Neurospora crassa by electron microscopy and conical tilt reconstruction. J Mol Biol 265:409–418

    Article  PubMed  Google Scholar 

  • Hatefi M, Haavik AG, Griffiths DE (1962) Studies of the electron transfer system. XL. Preparation and properties of mitochondrial DPNH-coenzyme Q reductase. J Biol Chem 237:1676–1680

    PubMed  CAS  Google Scholar 

  • Hattori N, Suzuki H, Wang Y, Minoshima S, Shimizu N, Yoshino H, Kurashima R, Tanaka M, Ozawa T, Mizuno Y (1995) Structural organization and chromosomal localization of the human nuclear gene (NDUFV2) for the 24 kDa iron-sulfur subunit of complex I in mitochondrial respiratory chain. Biochem Biophys Res Commun 216:771–777

    Article  PubMed  CAS  Google Scholar 

  • Hofhaus G, Johns D, Hurko O, Attardi G, Chomyn A (1996) Respiration and growth defects in transmitochondrial cell lines carrying the 11778 mutation associated with Leber’s hereditary optic neuropathy. J Biol Chem 271:13155–13161

    Article  PubMed  CAS  Google Scholar 

  • Hollingworth RM, Ahammadsahib KI (1995) Inhibitors of respiratory complex I: mechanisms, pesticidal actions and toxicology. Rev Pestic Toxicol 3:277–302

    CAS  Google Scholar 

  • Holt IJ, Harding AE, Morgan-Hughes JA (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717–719

    Article  PubMed  CAS  Google Scholar 

  • Hyslop SJ, Duncan AMV, Pitkänen S, Robinson BH (1996) Assigment of the PSST subunit gene of human mitochondrial complex I to chromosome 19pl3. Genomics 37:375–380

    Article  PubMed  CAS  Google Scholar 

  • King M, Attardi G (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246:500–503

    Article  PubMed  CAS  Google Scholar 

  • Lestienne P, Ponsot G (1988) Kearn-Sayres syndrome with muscle mitochondrial DNA deletion. Lancet 1:885

    Article  PubMed  CAS  Google Scholar 

  • Majander A, Huoponen K, Savontaus ML, Nikoskelainen E, Wikström M (1991) Electron transfer properties of NADH:ubiquinone reductase in the Ndl/3460 and the Nd4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON). FEBS Lett 292:289–292

    Article  PubMed  CAS  Google Scholar 

  • Majander A, Finel M, Savontaus MJ, Nikoskelainen E, Wikström M (1996) Catalytic activity of complex I in cell lines that possess replacement mutations in the ND genes in Leber’s hereditary optic neuropathy. Eur J Biochem 239:201–207

    Article  PubMed  CAS  Google Scholar 

  • Matsunaga T, Kudo J, Takahashi K, Dohmen K, Hayashida K, Okamura S, Ishibashi H, Niho Y (1996) Rotenone, a mitochondrial NADH dehydrogenase inhibitor, induces cell surface expression of CD 13 and CD38 and apoptosis in HL-60 cells. Leuk Lymphoma 20:487–494

    Article  PubMed  CAS  Google Scholar 

  • Moreadith RW, Cleeter MWJ, Ragan CI, Batshaw ML, Lehninger AL (1987) Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I. J Clin Invest 79:487–494

    Article  Google Scholar 

  • Papa S, Skulachev VP (1997) Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem 174:305–319

    Article  PubMed  CAS  Google Scholar 

  • Pata I, Tensing K, Metspalu A (1997) A human cDNA encoding the homologue of NADH:ubiquinone oxidoreductase subunit B13. Biochim Biophys Acta 1350:115–118

    PubMed  CAS  Google Scholar 

  • Procaccio V, Depetris D, Soularue P, Mattei MG, Lunardi J, Issartel JP (1997) cDNA sequence and chromosomal localization of the NDUFS8 human gene coding for the 23 kDa subunit of the mitochondrial complex I. Biochim Biophys Acta 1351:37–41

    Google Scholar 

  • Procaccio V, de Sury R, Martinez P, Depetris D, Rabilloud T, Soularue P, Lunardi J, Issartel JP (1998) Mapping to lq23 of the human gene (NDUFS2) encoding the 49 kDa subunit of the mitochondrial respiratory complex I and immunodetection of the mature protein in mitochondria. Mammal Genome 9:482–484

    Article  CAS  Google Scholar 

  • Ramsay RR, Krueger MJ, Youngster SK, Gluck MR, Casida JE, Singer TP (1991) Interaction of -methyl-4-phenylpyridinium ion (MPP+) and its analogs with the rotenone/piericidin binding site of NADH dehydrogenase. J Neurochem 56:1184–1190

    Article  PubMed  CAS  Google Scholar 

  • Robinson BH (1998) Human complex I deficiencyxlinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defects. Biochim Biophys Acta 1364:271–286

    Article  PubMed  CAS  Google Scholar 

  • Russell MW, duManoir S, Collins FS, Brody LC (1997) Cloning of the human NADH:ubiquinone oxidoreductase subunit B13: localization to chromosome 7q32 and identification of a pseudogene on 11p 15. Mammal Genome 8:60–61

    Article  CAS  Google Scholar 

  • Shinenaga MK, Hagen TM, Ames BM (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91:10771–10778

    Article  Google Scholar 

  • Sled’ VD, Friedrich T, Leif H, Weiss H, Meinhardt SW, Fukumori Y, Calhoun MW, Gennis RB, Ohnishi T (1993) Bacterial NADH-quinone oxidoreductases: iron-sulfur clusters and related problems. J Bioenerg Biomembr 25:347–356

    Article  Google Scholar 

  • Spencer SR, Taylor JB, Coll IG, Xia CL, Pemble SE, Ketterer B (1992) The human mitochondrial NADH.ubiquinone oxidoreductase 51-kDA subunit maps adjacent to the glutathione Stransferase Pl-1 gene on chromosome llql3. Genomics 14:1116–1118

    Article  PubMed  CAS  Google Scholar 

  • van den Heuvel L, Ruitenbeek W, Smeets R, Gelman-Kohan Z, Elpeleg O, Loeffen J, Trijbels F, Mariman E, de Bruijn D, Smeitink J (1998) Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit. Am J Human Genet 62:262–268

    Article  Google Scholar 

  • Walker JE (1992) The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains. Q Rev Biophys 25:253–324

    Article  PubMed  CAS  Google Scholar 

  • Weidner U, Geier S, Ptock A, Friedrich T, Leif H, Weiss H (1993) The gene locus of the protontranslocating NADH-ubiquinone oxidoreductase in Escherichia coli. Organization of the 14 genes and relationship between the derived proteins and subunits of mitochondrial complex I. J Mol Biol 233:109–122

    Article  PubMed  CAS  Google Scholar 

  • Yagi T, Yano T, Matsuno-Yagi A (1993) Characteristics of the energy-transducing NADH-qui-none oxidoreductase of Paracoccus denitrificans as revealed by biochemical, biophysical and molecular biological approaches. J Bioenerg Biomembr 25:339–345

    Article  PubMed  CAS  Google Scholar 

  • Yano T, Chu SS, Sled’ VD, Ohnishi T, Yagi T (1997) The proton-translocation NADH-quinone oxidoreductase (NDH-1) of thermophilic bacterium Thermus thermophilus HB-8. J Biol Chem 272:4201–4211

    Article  PubMed  CAS  Google Scholar 

  • Zhuchenko O, Wehnert M, Bailey J, Sun ZS, Lee CC (1996) Isolation, mapping, and genomic structure of an X-linked gene for a subunit of human mitochondrial complex I. Genomics 37:281–288

    Article  PubMed  CAS  Google Scholar 

  • Zickermann V, Barquera B, Wikström M, Finel M (1998) Analysis of the pathogenic human mitochondrial mutation ND1/3460, and mutations of strictly conserved residues in its vicinity, using the bacterium Paracoccus denitrificans. Biochemistry 37:11792–11796

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratoire de BioEnergétique Cellulaire et Pathologique, EA UJF 2411, DBMS/CE A Grenoble, 17 rue des Martyrs, 38054, Grenoble Cedex 9, France

    H. Duborjal, R. Beugnot, V. Procaccio, J. P. Issartel & J. Lunardi

  2. Biochimie de l’ADN, CHU Grenoble, 38043, Grenoble Cedex, France

    V. Procaccio & J. Lunardi

Authors
  1. H. Duborjal
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  2. R. Beugnot
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  3. V. Procaccio
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  4. J. P. Issartel
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  5. J. Lunardi
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Editors and Affiliations

  1. E 99-29 INSERM, Physiologie Mitochondriale, Université Victor Segalen Bordeaux 2, 146, rue Léo Saignat, 33076, Bordeaux Cedex, France

    Patrick Lestienne (Directeur de Recherche INSERM) (Directeur de Recherche INSERM)

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© 1999 Springer-Verlag Berlin Heidelberg

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Duborjal, H., Beugnot, R., Procaccio, V., Issartel, J.P., Lunardi, J. (1999). Structure, Function and Pathology of Complex I. In: Lestienne, P. (eds) Mitochondrial Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59884-5_6

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  • DOI: https://doi.org/10.1007/978-3-642-59884-5_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64166-4

  • Online ISBN: 978-3-642-59884-5

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