Eukaryotic complex I: functional diversity and experimental systems to unravel the assembly process

  • Claire Remacle
  • M. Rosario Barbieri
  • Pierre Cardol
  • Patrice P. Hamel


With more than 40 subunits, one FMN co-factor and eight FeS clusters, complex I or NADH:ubiquinone oxidoreductase is the largest multimeric respiratory enzyme in the mitochondria. In this review, we focus on the diversity of eukaryotic complex I. We describe the additional activities that have been reported to be associated with mitochondrial complex I and discuss their physiological significance. The recent identification of complex I-like enzymes in the hydrogenosome, a mitochondria-derived organelle is also discussed here. Complex I assembly in the mitochondrial inner membrane is an intricate process that requires the cooperation of the nuclear and mitochondrial genomes. The most prevalent forms of mitochondrial dysfunction in humans are deficiencies in complex I and remarkably, the molecular basis for 60% of complex I-linked defects is currently unknown. This suggests that mutations in yet-to-be-discovered assembly genes should exist. We review the different experimental systems for the study of complex I assembly. To our knowledge, in none of them, large screenings of complex I mutants have been performed. We propose that the unicellular green alga Chlamydomonas reinhardtii is a promising system for such a study. Complex I mutants can be easily scored on a phenotypical basis and a large number of transformants generated by insertional mutagenesis can be screened, which opens the possibility to find new genes involved in the assembly of the enzyme. Moreover, mitochondrial transformation, a recent technological advance, is now available, allowing the manipulation of all five complex I mitochondrial genes in this organism.


Mitochondria Human disease Complex I Assembly factors Mitochondrial transformation Model systems Chlamydomonas 



Research projects in the authors’ laboratories are funded by a United Mitochondrial Disease Foundation research grant (P. H. and C. R.), grants 2.4582.05 and from FNRS, Fonds Spéciaux pour la Recherche Universitaire (C. R.), and the College of Biological Sciences, the College of Medical and Public Health, and the Dorothy M. Davis Heart and Lung Institute at The Ohio State University (P. H.). P. H. also wishes to acknowledge the Institute of Mitochondrial Biology at The Ohio State University for intellectual support. C. R. was supported by a sabbatical grant from FNRS during her stay at Ohio State University (Summer 2006 and 2007). P. C. is a postdoctoral researcher from FNRS. The authors wish to thank Dr. Brett H. Graham for sharing unpublished results, Dr. Birgit Alber, Dr. Yeong-Reen Chen and Sara Cline for critical reading of the manuscript.


  1. Abdrakhmanova A, Dobrynin K, Zwicker K, Kerscher S, Brandt U (2005) Functional sulfurtransferase is associated with mitochondrial complex I from Yarrowia lipolytica, but is not required for assembly of its iron–sulfur clusters. FEBS Lett 579:6781–6785PubMedGoogle Scholar
  2. Abdrakhmanova A, Zickermann V, Bostina M, Radermacher M, Schagger H, Kerscher S, Brandt U (2004) Subunit composition of mitochondrial complex I from the yeast Yarrowia lipolytica. Biochim Biophys Acta 1658:148–156PubMedGoogle Scholar
  3. Acin-Perez R, Bayona-Bafaluy MP, Fernandez-Silva P, Moreno-Loshuertos R, Perez-Martos A, Bruno C, Moraes CT, Enriquez JA (2004) Respiratory complex III is required to maintain complex I in mammalian mitochondria. Mol Cell 13:805–815PubMedGoogle Scholar
  4. Ahlers PM, Garofano A, Kerscher SJ, Brandt U (2000) Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic model to analyse Leigh syndrome mutations in the complex I core subunits PSST and TYKY. Biochim Biophys Acta 1459:258–265PubMedGoogle Scholar
  5. Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV (2000) Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. J Biol Chem 275:33416–33426PubMedGoogle Scholar
  6. Antonicka H, Ogilvie I, Taivassalo T, Anitori RP, Haller RG, Vissing J, Kennaway NG, Shoubridge EA (2003) Identification and characterization of a common set of complex I assembly intermediates in mitochondria from patients with complex I deficiency. J Biol Chem 278:43081–43088PubMedGoogle Scholar
  7. Barrientos A, Barros MH, Valnot I, Rotig A, Rustin P, Tzagoloff A (2002) Cytochrome oxidase in health and disease. Gene 286:53–63PubMedGoogle Scholar
  8. Batandier C, Picard A, Tessier N, Lunardi J (2000) Identification of a novel T398A mutation in the ND5 subunit of the mitochondrial complex I and of three novel mtDNA polymorphisms in two patients presenting ocular symptoms. Hum Mutat 16:532PubMedGoogle Scholar
  9. Bellomo F, Piccoli C, Cocco T, Scacco S, Papa F, Gaballo A, Boffoli D, Signorile A, D’Aprile A, Scrima R, Sardanelli AM, Capitanio N, Papa S (2006) Regulation by the cAMP cascade of oxygen free radical balance in mammalian cells. Antioxid Redox Signal 8:495–502PubMedGoogle Scholar
  10. Blacque OE, Cevik S, Kaplan OI (2008) Intraflagellar transport: from molecular characterisation to mechanism. Front Biosci 13:2633–2652PubMedGoogle Scholar
  11. Boxma B, de Graaf RM, van der Staay GW, van Alen TA, Ricard G, Gabaldon T, van Hoek AH, Moon-van der Staay SY, Koopman WJ, van Hellemond JJ, Tielens AG, Friedrich T, Veenhuis M, Huynen MA, Hackstein JH (2005) An anaerobic mitochondrion that produces hydrogen. Nature 434:74–79PubMedGoogle Scholar
  12. Bradley PJ, Lahti CJ, Plumper E, Johnson PJ (1997) Targeting and translocation of proteins into the hydrogenosome of the protist Trichomonas: similarities with mitochondrial protein import. EMBO J 16:3484–3493PubMedGoogle Scholar
  13. Brangeon J, Sabar M, Gutierres S, Combettes B, Bove J, Gendy C, Chetrit P, des Francs-Small CC, Pla M, Vedel F, De Paepe R (2000) Defective splicing of the first nad4 intron is associated with lack of several complex I subunits in the Nicotiana sylvestris NMS1 nuclear mutant. Plant J 21:269–280PubMedGoogle Scholar
  14. Braun HP, Schmitz UK (1995) The bifunctional cytochrome c reductase/processing peptidase complex from plant mitochondria. J Bioenerg Biomembr 27:423–436PubMedGoogle Scholar
  15. Braun HP, Zabaleta E (2007) Carbonic anhydrase subunits of the mitochondrial NADH dehydrogenase complex (complex I) in plants. Physiol Plant 129:114–122Google Scholar
  16. Bulteau A-L, O’Neill HA, Kennedy MC, Ikeda-Saito M, Isaya G, Szweda LI (2004) Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 305:242–245PubMedGoogle Scholar
  17. Byers DM, Gong H (2007) Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family. Biochem Cell Biol 85:649–662PubMedGoogle Scholar
  18. Cardol P, Boutaffala L, Memmi S, Devreese B, Matagne RF, Remacle C (2008) In Chlamydomonas, the loss of ND5 subunit prevents the assembly of whole mitochondrial complex I and leads to the formation of a low abundant 700 kDa subcomplex. Biochimica et Biophysica Acta (BBA)—Bioenergetics 1777:388–396Google Scholar
  19. Cardol P, Gonzalez-Halphen D, Reyes-Prieto A, Baurain D, Matagne RF, Remacle C (2005) The mitochondrial oxidative phosphorylation proteome of Chlamydomonas reinhardtii deduced from the Genome Sequencing Project. Plant Physiol 137:447–459PubMedGoogle Scholar
  20. Cardol P, Lapaille M, Minet P, Franck F, Matagne RF, Remacle C (2006) ND3 and ND4L subunits of mitochondrial complex I, both nucleus encoded in Chlamydomonas reinhardtii, are required for activity and assembly of the enzyme. Eukaryot Cell 5:1460–1467PubMedGoogle Scholar
  21. Cardol P, Matagne RF, Remacle C (2002) Impact of mutations affecting ND mitochondria-encoded subunits on the activity and assembly of complex I in Chlamydomonas. Implication for the structural organization of the enzyme. J Mol Biol 319:1211–1221PubMedGoogle Scholar
  22. Cardol P, Vanrobaeys F, Devreese B, Van Beeumen J, Matagne RF, Remacle C (2004) Higher plant-like subunit composition of mitochondrial complex I from Chlamydomonas reinhardtii: 31 conserved components among eukaryotes. Biochim Biophys Acta 1658:212–224PubMedGoogle Scholar
  23. Carroll J, Fearnley IM, Shannon RJ, Hirst J, Walker JE (2003) Analysis of the subunit composition of complex I from bovine heart mitochondria. Mol Cell Proteomics 2:117–126PubMedGoogle Scholar
  24. Carroll J, Shannon RJ, Fearnley IM, Walker JE, Hirst J (2002) Definition of the nuclear encoded protein composition of bovine heart mitochondrial complex I. Identification of two new subunits. J Biol Chem 277:50311–50317PubMedGoogle Scholar
  25. Cermakova P, Zk Verner, Man P, Lukes J, Horvath A (2007) Characterization of the NADH:ubiquinone oxidoreductase (complex I) in the trypanosomatid Phytomonas serpens (Kinetoplastida). FEBS J 274:3150–3158PubMedGoogle Scholar
  26. Chen R, Fearnley IM, Peak-Chew SY, Walker JE (2004) The phosphorylation of subunits of complex I from bovine heart mitochondria. J Biol Chem 279:26036–26045PubMedGoogle Scholar
  27. Cipollone R, Ascenzi P, Visca P (2007) Common themes and variations in the rhodanese superfamily. IUBMB Life 59:51–59PubMedGoogle Scholar
  28. Cittadella R, Andreoli V, Manna I, Oliveri RL, Quattrone A (2001) A new human mtDNA polymorphism: MTND6: 14562 (C- > T). Hum Mutat 17:238PubMedGoogle Scholar
  29. Crimi M, Sciacco M, Galbiati S, Bordoni A, Malferrari G, Del Bo R, Biunno I, Bresolin N, Comi GP (2002) A collection of 33 novel human mtDNA homoplasmic variants. Hum Mutat 20:409PubMedGoogle Scholar
  30. Cronan JE, Fearnley IM, Walker JE (2005) Mammalian mitochondria contain a soluble acyl carrier protein. FEBS Lett 579:4892–4896PubMedGoogle Scholar
  31. de Longevialle AF, Meyer EH, Andres C, Taylor NL, Lurin C, Millar AH, Small ID (2007) The pentatricopeptide repeat gene OTP43 is required for trans-splicing of the mitochondrial nad1 intron 1 in Arabidopsis thaliana. Plant Cell 19:3256–3265PubMedGoogle Scholar
  32. De Rasmo D, Panelli D, Sardanelli AM, Papa S (2008) cAMP-dependent protein kinase regulates the mitochondrial import of the nuclear encoded NDUFS4 subunit of complex I. Cell Signal 20:989–997PubMedGoogle Scholar
  33. DeCorby A, Gaskova D, Sayles LC, Lemire BD (2007) Expression of Ndi1p, an alternative NADH:ubiquinone oxidoreductase, increases mitochondrial membrane potential in a C. elegans model of mitochondrial disease. Biochimica et Biophysica Acta (BBA)—Bioenergetics 1767:1157–1163Google Scholar
  34. Diaz F, Fukui H, Garcia S, Moraes CT (2006) Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts. Mol Cell Biol 26:4872–4881PubMedGoogle Scholar
  35. Djafarzadeh R, Kerscher S, Zwicker K, Radermacher M, Lindahl M, Schagger H, Brandt U (2000) Biophysical and structural characterization of proton-translocating NADH-dehydrogenase (complex I) from the strictly aerobic yeast Yarrowia lipolytica. Biochim Biophys Acta 1459:230–238PubMedGoogle Scholar
  36. Duarte M, Mota N, Pinto L, Videira A (1998) Inactivation of the gene coding for the 30.4-kDa subunit of respiratory chain NADH dehydrogenase: is the enzyme essential for Neurospora? Mol Gen Genet 257:368–375PubMedGoogle Scholar
  37. Duarte M, Schulte U, Ushakova AV, Videira A (2005) Neurospora strains harboring mitochondrial disease-associated mutations in iron–sulfur subunits of complex I. Genetics 171:91–99PubMedGoogle Scholar
  38. Duarte M, Sousa R, Videira A (1995) Inactivation of genes encoding subunits of the peripheral and membrane arms of neurospora mitochondrial complex I and effects on enzyme assembly. Genetics 139:1211–1221PubMedGoogle Scholar
  39. Duarte M, Videira A (2000) Respiratory chain complex I is essential for sexual development in neurospora and binding of iron–sulfur clusters are required for enzyme assembly. Genetics 156:607–615PubMedGoogle Scholar
  40. Duby F, Matagne RF (1999) Alteration of dark respiration and reduction of phototrophic growth in a mitochondrial DNA deletion mutant of Chlamydomonas lacking cob, nd4, and the 3′ end of nd5. Plant Cell 11:115–125PubMedGoogle Scholar
  41. Dunning CJ, McKenzie M, Sugiana C, Lazarou M, Silke J, Connelly A, Fletcher JM, Kirby DM, Thorburn DR, Ryan MT (2007) Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease. EMBO J 26:3227–3237PubMedGoogle Scholar
  42. Dyall SD, Johnson PJ (2000) Origins of hydrogenosomes and mitochondria: evolution and organelle biogenesis. Curr Opin Microbiol 3:404–411PubMedGoogle Scholar
  43. Dyall SD, Yan W, Delgadillo-Correa MG, Lunceford A, Loo JA, Clarke CF, Johnson PJ (2004) Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex. Nature 431:1103–1107PubMedGoogle Scholar
  44. Fearnley IM, Carroll J, Shannon RJ, Runswick MJ, Walker JE, Hirst J (2001) GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I). J Biol Chem 276:38345–38348PubMedGoogle Scholar
  45. Fearnley IM, Carroll J, Walker JE (2007) Proteomic analysis of the subunit composition of complex I (NADH:ubiquinone oxidoreductase) from bovine heart mitochondria. Methods Mol Biol 357:103–125PubMedGoogle Scholar
  46. Fernandez-Moreira D, Ugalde C, Smeets R, Rodenburg RJ, Lopez-Laso E, Ruiz-Falco ML, Briones P, Martin MA, Smeitink JA, Arenas J (2007) X-linked NDUFA1 gene mutations associated with mitochondrial encephalomyopathy. Ann Neurol 61:73–83PubMedGoogle Scholar
  47. Finel M, Skehel JM, Albracht SP, Fearnley IM, Walker JE (1992) Resolution of NADH:ubiquinone oxidoreductase from bovine heart mitochondria into two subcomplexes, one of which contains the redox centers of the enzyme. Biochemistry 31:11425–11434PubMedGoogle Scholar
  48. Fontanesi F, Soto IC, Horn D, Barrientos A (2006) Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular process. Am J Physiol Cell Physiol 291:C1129–C1147PubMedGoogle Scholar
  49. Friedrich T (1998) The NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli. Biochim Biophys Acta 1364:134–146PubMedGoogle Scholar
  50. Friedrich T, Bottcher B (2004) The gross structure of the respiratory complex I: a Lego System. Biochim Biophys Acta 1608:1–9PubMedGoogle Scholar
  51. Gabaldon T, Rainey D, Huynen MA (2005) Tracing the evolution of a large protein complex in the eukaryotes, NADH:ubiquinone oxidoreductase (Complex I). J Mol Biol 348:857–870PubMedGoogle Scholar
  52. Galante YM, Hatefi Y (1978) Resolution of complex I and isolation of NADH dehydrogenase and an iron–sulfur protein. Methods Enzymol 53:15–21PubMedGoogle Scholar
  53. Gohre V, Ossenbuhl F, Crevecoeur M, Eichacker LA, Rochaix J-D (2006) One of Two Alb3 Proteins Is Essential for the Assembly of the Photosystems and for Cell Survival in Chlamydomonas. Plant Cell 18:1454–1466PubMedGoogle Scholar
  54. González-Halphen D, Maslov D (2004) NADH-ubiquinone oxidoreductase activity in the kinetoplasts of the plant trypanosomatid Phytomonas serpens. Parasitol Res 92:341–346PubMedGoogle Scholar
  55. Grad LI, Lemire BD (2004) Mitochondrial complex I mutations in Caenorhabditis elegans produce cytochrome c oxidase deficiency, oxidative stress and vitamin-responsive lactic acidosis. Hum Mol Genet 13:303–314PubMedGoogle Scholar
  56. Grad LI, Sayles LC, Lemire BD (2005) Introduction of an additional pathway for lactate oxidation in the treatment of lactic acidosis and mitochondrial dysfunction in Caenorhabditis elegans. Proc Natl Acad Sci USA 102:18367–18372PubMedGoogle Scholar
  57. Grigorieff N (1998) Three-dimensional structure of bovine NADH:ubiquinone oxidoreductase (complex I) at 22 A in ice. J Mol Biol 277:1033–1046PubMedGoogle Scholar
  58. Grossman AR, Croft M, Gladyshev VN, Merchant SS, Posewitz MC, Prochnik S, Spalding MH (2007) Novel metabolism in Chlamydomonas through the lens of genomics. Curr Opin Plant Biol 10:190–198PubMedGoogle Scholar
  59. Grossman AR, Harris EE, Hauser C, Lefebvre PA, Martinez D, Rokhsar D, Shrager J, Silflow CD, Stern D, Vallon O, Zhang Z (2003) Chlamydomonas reinhardtii at the crossroads of genomics. Eukaryot Cell 2:1137–1150PubMedGoogle Scholar
  60. Guenebaut V, Schlitt A, Weiss H, Leonard K, Friedrich T (1998) Consistent structure between bacterial and mitochondrial NADH:ubiquinone oxidoreductase (complex I). J Mol Biol 276:105–112PubMedGoogle Scholar
  61. Guenebaut 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 265:409–418PubMedGoogle Scholar
  62. Harris EH (2001) CHLAMYDOMONAS AS A MODEL ORGANISM. Annu Rev Plant Physiol Plant Mol Biol 52:363–406PubMedGoogle Scholar
  63. Heazlewood JL, Howell KA, Millar AH (2003) Mitochondrial complex I from Arabidopsis and rice: orthologs of mammalian and fungal components coupled with plant-specific subunits. Biochim Biophys Acta 1604:159–169PubMedGoogle Scholar
  64. Hinchliffe P, Carroll J, Sazanov LA (2006) Identification of a novel subunit of respiratory complex I from Thermus thermophilus. Biochemistry 45:4413–4420PubMedGoogle Scholar
  65. Hinchliffe P, Sazanov LA (2005) Organization of iron–sulfur clusters in respiratory complex I. Science 309:771–774PubMedGoogle Scholar
  66. Hirst J, Carroll J, Fearnley IM, Shannon RJ, Walker JE (2003) The nuclear encoded subunits of complex I from bovine heart mitochondria. Biochim Biophys Acta 1604:135–150PubMedGoogle Scholar
  67. Hofhaus G, Attardi G (1993) Lack of assembly of mitochondrial DNA-encoded subunits of respiratory NADH dehydrogenase and loss of enzyme activity in a human cell mutant lacking the mitochondrial ND4 gene product. EMBO J 12:3043–3048PubMedGoogle Scholar
  68. Hofhaus G, Johns DR, 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 271:13155–13161PubMedGoogle Scholar
  69. Hofhaus G, Weiss H, Leonard K (1991) Electron microscopic analysis of the peripheral and membrane parts of mitochondrial NADH dehydrogenase (complex I). J Mol Biol 221:1027–1043PubMedGoogle Scholar
  70. Horner DS, Foster PG, Embley TM (2000) Iron Hydrogenases and the Evolution of Anaerobic Eukaryotes. Mol Biol Evol 17:1695–1709PubMedGoogle Scholar
  71. Hrdy I, Cammack R, Stopka P, Kulda J, Tachezy J (2005) Alternative pathway of metronidazole activation in Trichomonas vaginalis hydrogenosomes. Antimicrob Agents Chemother 49:5033–5036PubMedGoogle Scholar
  72. Hrdy I, Hirt RP, Dolezal P, Bardonova L, Foster PG, Tachezy J, Martin Embley T (2004) Trichomonas hydrogenosomes contain the NADH dehydrogenase module of mitochondrial complex I. Nature 432:618–622PubMedGoogle Scholar
  73. Jain M, Shrager J, Harris EH, Halbrook R, Grossman AR, Hauser C, Vallon O (2007) EST assembly supported by a draft genome sequence: an analysis of the Chlamydomonas reinhardtii transcriptome. Nucleic Acids Res 35:2074–2083PubMedGoogle Scholar
  74. Janssen RJ, Nijtmans LG, van den Heuvel LP, Smeitink JA (2006) Mitochondrial complex I: structure, function and pathology. J Inherit Metab Dis 29:499–515PubMedGoogle Scholar
  75. Joza N, Oudit GY, Brown D, Benit P, Kassiri Z, Vahsen N, Benoit L, Patel MM, Nowikovsky K, Vassault A, Backx PH, Wada T, Kroemer G, Rustin P, Penninger JM (2005) Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy. Mol Cell Biol 25:10261–10272PubMedGoogle Scholar
  76. Kao MC, Di Bernardo S, Nakamaru-Ogiso E, Miyoshi H, Matsuno-Yagi A, Yagi T (2005) Characterization of the membrane domain subunit NuoJ (ND6) of the NADH-quinone oxidoreductase from Escherichia coli by chromosomal DNA manipulation. Biochemistry 44:3562–3571PubMedGoogle Scholar
  77. Kao MC, Di Bernardo S, Perego M, Nakamaru-Ogiso E, Matsuno-Yagi A, Yagi T (2004) Functional roles of four conserved charged residues in the membrane domain subunit NuoA of the proton-translocating NADH-quinone oxidoreductase from Escherichia coli. J Biol Chem 279:32360–32366PubMedGoogle Scholar
  78. Karp CM, Shukla MN, Buckley DJ, Buckley AR (2007) HRPAP20: a novel calmodulin-binding protein that increases breast cancer cell invasion. Oncogene 26:1780–1788PubMedGoogle Scholar
  79. Karpova OV, Newton KJ (1999) A partially assembled complex I in NAD4-deficient mitochondria of maize. Plant J 17:511–521Google Scholar
  80. Kerscher S, Drose S, Zwicker K, Zickermann V, Brandt U (2002) Yarrowia lipolytica, a yeast genetic system to study mitochondrial complex I. Biochim Biophys Acta 1555:83–91PubMedGoogle Scholar
  81. Kerscher S, Grgic L, Garofano A, Brandt U (2004) Application of the yeast Yarrowia lipolytica as a model to analyse human pathogenic mutations in mitochondrial complex I (NADH:ubiquinone oxidoreductase). Biochim Biophys Acta 1659:197–205PubMedGoogle Scholar
  82. Kerscher S, Kashani-Poor N, Zwicker K, Zickermann V, Brandt U (2001a) Exploring the catalytic core of complex I by Yarrowia lipolytica yeast genetics. J Bioenerg Biomembr 33:187–196PubMedGoogle Scholar
  83. Kerscher SJ, Eschemann A, Okun PM, Brandt U (2001b) External alternative NADH:ubiquinone oxidoreductase redirected to the internal face of the mitochondrial inner membrane rescues complex I deficiency in Yarrowia lipolytica. J Cell Sci 114:3915–3921PubMedGoogle Scholar
  84. Kerscher SJ, Okun JG, Brandt U (1999) A single external enzyme confers alternative NADH:ubiquinone oxidoreductase activity in Yarrowia lipolytica. J Cell Sci 112(Pt 14):2347–2354PubMedGoogle Scholar
  85. Kiefer D, Kuhn A (2007) YidC as an essential and multifunctional component in membrane protein assembly. Int Rev Cytol 259:113–138PubMedCrossRefGoogle Scholar
  86. Kirby DM, Crawford M, Cleary MA, Dahl HH, Dennett X, Thorburn DR (1999) Respiratory chain complex I deficiency: an underdiagnosed energy generation disorder. Neurology 52:1255–1264PubMedGoogle Scholar
  87. Kuffner R, Rohr A, Schmiede A, Krull C, Schulte U (1998) Involvement of two novel chaperones in the assembly of mitochondrial NADH:Ubiquinone oxidoreductase (complex I). J Mol Biol 283:409–417PubMedGoogle Scholar
  88. Lazarou M, McKenzie M, Ohtake A, Thorburn DR, Ryan MT (2007) Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I. Mol Cell Biol 27:4228–4237PubMedGoogle Scholar
  89. Lee B-h, Lee H, Xiong L, Zhu J-K (2002) A mitochondrial complex I defect impairs cold-regulated nuclear gene expression. Plant Cell 14:1235–1251PubMedGoogle Scholar
  90. Lezhneva L, Amann K, Meurer J (2004) The universally conserved HCF101 protein is involved in assembly of [4Fe-4S]-cluster-containing complexes in Arabidopsis thaliana chloroplasts. Plant J 37:174–185PubMedGoogle Scholar
  91. Li Y, D’Aurelio M, Deng J-H, Park J-S, Manfredi G, Hu P, Lu J, Bai Y (2007) an assembled complex IV maintains the stability and activity of complex I in mammalian mitochondria. J Biol Chem 282:17557–17562PubMedGoogle Scholar
  92. Loeffen JL, Smeitink JA, Trijbels JM, Janssen AJ, Triepels RH, Sengers RC, van den Heuvel LP (2000) Isolated complex I deficiency in children: clinical, biochemical and genetic aspects. Hum Mutat 15:123–134PubMedGoogle Scholar
  93. Lu H, Cao X (2008) GRIM-19 is essential for maintenance of mitochondrial membrane potential. Mol. Biol. Cell:E07-07-0683Google Scholar
  94. Lunardi J, Darrouzet E, Dupuis A, Issartel JP (1998) The nuoM arg368his mutation in NADH:ubiquinone oxidoreductase from Rhodobacter capsulatus: a model for the human nd4–11778 mtDNA mutation associated with Leber’s hereditary optic neuropathy. Biochim Biophys Acta 1407:114–124PubMedGoogle Scholar
  95. Ma J, Peng L, Guo J, Lu Q, Lu C, Zhang L (2007) LPA2 is required for efficient assembly of photosystem II in Arabidopsis thaliana. Plant Cell 19:1980–1993PubMedGoogle Scholar
  96. Maeda S-i, Badger MR, Price GD (2002) Novel gene products associated with NdhD3/D4-containing NDH-1 complexes are involved in photosynthetic CO2 hydration in the cyanobacterium, Synechococcus sp. PCC7942. Mol Microbiol 43:425–435PubMedGoogle Scholar
  97. Malfatti E, Bugiani M, Invernizzi F, de Souza CF-M, Farina L, Carrara F, Lamantea E, Antozzi C, Confalonieri P, Sanseverino MT, Giugliani R, Uziel G, Zeviani M (2007) Novel mutations of ND genes in complex I deficiency associated with mitochondrial encephalopathy. Brain:awm114Google Scholar
  98. Maximo V, Lima J, Soares P, Silva A, Bento I, Sobrinho-Simoes M (2008) GRIM-19 in health and disease. Adv Anat Pathol 15:46–53PubMedGoogle Scholar
  99. Melo AM, Bandeiras TM, Teixeira M (2004) New insights into type II NAD(P) H:quinone oxidoreductases. Microbiol Mol Biol Rev 68:603–616PubMedGoogle Scholar
  100. Merchant SS, Prochnik SE, Vallon O, Harris EH, Karpowicz SJ, Witman GB, Terry A, Salamov A, Fritz-Laylin LK, Marechal-Drouard L, Marshall WF, Qu LH, Nelson DR, Sanderfoot AA, Spalding MH, Kapitonov VV, Ren Q, Ferris P, Lindquist E, Shapiro H, Lucas SM, Grimwood J, Schmutz J, Cardol P, Cerutti H, Chanfreau G, Chen CL, Cognat V, Croft MT, Dent R, Dutcher S, Fernandez E, Fukuzawa H, Gonzalez-Ballester D, Gonzalez-Halphen D, Hallmann A, Hanikenne M, Hippler M, Inwood W, Jabbari K, Kalanon M, Kuras R, Lefebvre PA, Lemaire SD, Lobanov AV, Lohr M, Manuell A, Meier I, Mets L, Mittag M, Mittelmeier T, Moroney JV, Moseley J, Napoli C, Nedelcu AM, Niyogi K, Novoselov SV, Paulsen IT, Pazour G, Purton S, Ral JP, Riano-Pachon DM, Riekhof W, Rymarquis L, Schroda M, Stern D, Umen J, Willows R, Wilson N, Zimmer SL, Allmer J, Balk J, Bisova K, Chen CJ, Elias M, Gendler K, Hauser C, Lamb MR, Ledford H, Long JC, Minagawa J, Page MD, Pan J, Pootakham W, Roje S, Rose A, Stahlberg E, Terauchi AM, Yang P, Ball S, Bowler C, Dieckmann CL, Gladyshev VN, Green P, Jorgensen R, Mayfield S, Mueller-Roeber B, Rajamani S, Sayre RT, Brokstein P, Dubchak I, Goodstein D, Hornick L, Huang YW, Jhaveri J, Luo Y, Martinez D, Ngau WC, Otillar B, Poliakov A, Porter A, Szajkowski L, Werner G, Zhou K, Grigoriev IV, Rokhsar DS, Grossman AR (2007) The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science 318:245–250PubMedGoogle Scholar
  101. Meyer EH, Heazlewood JL, Millar AH (2007) Mitochondrial acyl carrier proteins in Arabidopsis thaliana are predominantly soluble matrix proteins and none can be confirmed as subunits of respiratory Complex I. Plant Mol Biol 64:319–327PubMedGoogle Scholar
  102. Meyer EH, Taylor NL, Millar AH (2008) Resolving and identifying protein components of plant mitochondrial respiratory complexes using three dimensions of gel electrophoresis. J Proteome Res 7:786–794PubMedGoogle Scholar
  103. Millar AH, Mittova V, Kiddle G, Heazlewood JL, Bartoli CG, Theodoulou FL, Foyer CH (2003) Control of Ascorbate Synthesis by Respiration and Its Implications for Stress Responses. Plant Physiol 133:443–447PubMedGoogle Scholar
  104. Mueller EG (2006) Trafficking in persulfides: delivering sulfur in biosynthetic pathways. Nat Chem Biol 2:185–194PubMedGoogle Scholar
  105. Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, Ghosh SS, Capaldi RA (2003) The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. J Biol Chem 278:13619–13622PubMedGoogle Scholar
  106. Nakagawa N, Sakurai N (2006) A mutation in At-nMat1a, which encodes a nuclear gene having high similarity to group II intron maturase, causes impaired splicing of mitochondrial NAD4 transcript and altered carbon metabolism in Arabidopsis thaliana. Plant Cell Physiol 47:772–783PubMedGoogle Scholar
  107. Nargang FE, Preuss M, Neupert W, Herrmann JM (2002) The Oxa1 protein forms a homooligomeric complex and is an essential part of the mitochondrial export translocase in Neurospora crassa. J Biol Chem 277:12846–12853PubMedGoogle Scholar
  108. Nawathean P, Maslov DA (2000) The absence of genes for cytochrome c oxidase and reductase subunits in maxicircle kinetoplast DNA of the respiration-deficient plant trypanosomatid Phytomonas serpens. Curr Genet 38:95–103PubMedGoogle Scholar
  109. Ogilvie I, Kennaway NG, Shoubridge EA (2005) A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. J Clin Invest 115:2784–2792PubMedGoogle Scholar
  110. Ohnishi T (1998) Iron–sulfur clusters/semiquinones in Complex I. Biochimica et Biophysica Acta (BBA)—Bioenergetics 1364:186–206Google Scholar
  111. Ossenbuhl F, Inaba-Sulpice M, Meurer J, Soll J, Eichacker LA (2006) The synechocystis sp PCC 6803 oxa1 homolog is essential for membrane integration of reaction center precursor protein pD1. Plant Cell 18:2236–2246PubMedGoogle Scholar
  112. Palmisano G, Sardanelli AM, Signorile A, Papa S, Larsen MR (2007) The phosphorylation pattern of bovine heart complex I subunits. Proteomics 7:1575–1583PubMedGoogle Scholar
  113. Panigrahi AK, Zikova A, Dalley RA, Acestor N, Ogata Y, Anupama A, Myler PJ, Stuart KD (2008) Mitochondrial complexes in Trypanosoma brucei: a novel complex and a unique oxidoreductase complex. Mol Cell Proteomics 7:534–545PubMedGoogle Scholar
  114. Papa S (2002) The NDUFS4 nuclear gene of complex I of mitochondria and the cAMP cascade. Biochim Biophys Acta 1555:147–153PubMedGoogle Scholar
  115. Papa S, Sardanelli AM, Cocco T, Speranza F, Scacco SC, Technikova-Dobrova Z (1996) The nuclear-encoded 18 kDa (IP) AQDQ subunit of bovine heart complex I is phosphorylated by the mitochondrial cAMP-dependent protein kinase. FEBS Lett 379:299–301PubMedGoogle Scholar
  116. Papa S, Scacco S, Sardanelli AM, Petruzzella V, Vergari R, Signorile A, Technikova-Dobrova Z (2002) Complex I and the cAMP cascade in human physiopathology. Biosci Rep 22:3–16PubMedGoogle Scholar
  117. Parisi G, Perales M, Fornasari MS, Colaneri A, Gonzalez-Schain N, Gomez-Casati D, Zimmermann S, Brennicke A, Araya A, Ferry JG, Echave J, Zabaleta E (2004) Gamma carbonic anhydrases in plant mitochondria. Plant Mol Biol 55:193–207PubMedGoogle Scholar
  118. Pätsi J, Kervinen M, Finel M, Hassinen IE (2008) Leber hereditary optic neuropathy mutations in the ND6 subunit of mitochondrial complex I affect ubiquinone reduction kinetics in a bacterial model of the enzyme. Biochem J 409:129–137PubMedGoogle Scholar
  119. Peng G, Fritzsch G, Zickermann V, Schagger H, Mentele R, Lottspeich F, Bostina M, Radermacher M, Huber R, Stetter KO, Michel H (2003) Isolation, characterization and electron microscopic single particle analysis of the NADH:ubiquinone oxidoreductase (complex I) from the hyperthermophilic eubacterium Aquifex aeolicus. Biochemistry 42:3032–3039PubMedGoogle Scholar
  120. Perales M, Eubel H, Heinemeyer J, Colaneri A, Zabaleta E, Braun HP (2005) Disruption of a nuclear gene encoding a mitochondrial gamma carbonic anhydrase reduces complex I and supercomplex I + III2 levels and alters mitochondrial physiology in Arabidopsis. J Mol Biol 350:263–277PubMedGoogle Scholar
  121. Perales M, Parisi G, Fornasari MS, Colaneri A, Villarreal F, Gonzalez-Schain N, Echave J, Gomez-Casati D, Braun HP, Araya A, Zabaleta E (2004) Gamma carbonic anhydrase like complex interact with plant mitochondrial complex I. Plant Mol Biol 56:947–957PubMedGoogle Scholar
  122. Peters K, Dudkina NV, Jansch L, Braun HP, Boekema EJ (2008) A structural investigation of complex I and I + III(2) supercomplex from Zea mays at 11–13 A resolution: assignment of the carbonic anhydrase domain and evidence for structural heterogeneity within complex I. Biochim Biophys Acta 1777(1):84–93PubMedGoogle Scholar
  123. Piccoli C, Scacco S, Bellomo F, Signorile A, Iuso A, Boffoli D, Scrima R, Capitanio N, Papa S (2006) cAMP controls oxygen metabolism in mammalian cells. FEBS Lett 580:4539–4543PubMedGoogle Scholar
  124. Pitkanen S, Feigenbaum A, Laframboise R, Robinson BH (1996) NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings. J Inherit Metab Dis 19:675–686PubMedGoogle Scholar
  125. Pla M, Mathieu C, De Paepe R, Chetrit P, Vedel F (1995) Deletion of the last two exons of the mitochondrial nad7 gene results in lack of the NAD7 polypeptide in a Nicotiana sylvestris CMS mutant. Mol Gen Genet 248:79–88PubMedGoogle Scholar
  126. Plesofsky N, Gardner N, Videira A, Brambl R (2000) NADH dehydrogenase in Neurospora crassa contains myristic acid covalently linked to the ND5 subunit peptide. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research 1495:223–230Google Scholar
  127. Pocsfalvi G, Cuccurullo M, Schlosser G, Scacco S, Papa S, Malorni A (2007) Phosphorylation of B14.5a subunit from bovine heart complex I identified by titanium dioxide selective enrichment and shotgun proteomics. Mol Cell Proteomics 6:231–237PubMedGoogle Scholar
  128. Prieur I, Lunardi J, Dupuis A (2001) Evidence for a quinone binding site close to the interface between NUOD and NUOB subunits of Complex I. Biochim Biophys Acta 1504:173–178PubMedGoogle Scholar
  129. Qi X, Lewin AS, Hauswirth WW, Guy J (2003) Suppression of complex I gene expression induces optic neuropathy. Ann Neurol 53:198–205PubMedGoogle Scholar
  130. Qi X, Lewin AS, Sun L, Hauswirth WW, Guy J (2004) SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. Ann Neurol 56:182–191PubMedGoogle Scholar
  131. Rebeille F, Alban C, Bourguignon J, Ravanel S, Douce R (2007) The role of plant mitochondria in the biosynthesis of coenzymes. Photosynth Res 92:149–162PubMedGoogle Scholar
  132. Reeves MB, Davies AA, McSharry BP, Wilkinson GW, Sinclair JH (2007) Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science 316:1345–1348PubMedGoogle Scholar
  133. Reinders J, Wagner K, Zahedi RP, Stojanovski D, Eyrich B, van der Laan M, Rehling P, Sickmann A, Pfanner N, Meisinger C (2007) Profiling phosphoproteins of yeast mitochondria reveals a role of phosphorylation in assembly of the ATP synthase. Mol Cell Proteomics 6:1896–1906PubMedGoogle Scholar
  134. Remacle C, Baurain D, Cardol P, Matagne RF (2001a) Mutants of Chlamydomonas reinhardtii deficient in mitochondrial complex I: characterization of two mutations affecting the nd1 coding sequence. Genetics 158:1051–1060PubMedGoogle Scholar
  135. Remacle C, Cardol P, Coosemans N, Gaisne M, Bonnefoy N (2006) High-efficiency biolistic transformation of Chlamydomonas mitochondria can be used to insert mutations in complex I genes. Proc Natl Acad Sci USA 103:4771–4776PubMedGoogle Scholar
  136. Remacle C, Duby F, Cardol P, Matagne RF (2001b) Mutations inactivating mitochondrial genes in Chlamydomonas reinhardtii. Biochem Soc Trans 29:442–446PubMedGoogle Scholar
  137. Ruiz-Pesini E, Lott MT, Procaccio V, Poole JC, Brandon MC, Mishmar D, Yi C, Kreuziger J, Baldi P, Wallace DC (2007) An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nucl Acids Res 35:D823–D828PubMedGoogle Scholar
  138. Saada A, Edvardson S, Rapoport M, Shaag A, Amry K, Miller C, Lorberboum-Galski H, Elpeleg O (2008) C6ORF66 is an assembly factor of mitochondrial complex I. Am J Hum Genet 82:32–38PubMedGoogle Scholar
  139. Sackmann U, Zensen R, Rohlen D, Jahnke U, Weiss H (1991) The acyl-carrier protein in Neurospora crassa mitochondria is a subunit of NADH:ubiquinone reductase (complex I). Eur J Biochem 200:463–469PubMedGoogle Scholar
  140. Sardanelli AM, Technikova-Dobrova Z, Scacco SC, Speranza F, Papa S (1995) Characterization of proteins phosphorylated by the cAMP-dependent protein kinase of bovine heart mitochondria. FEBS Lett 377:470–474PubMedGoogle Scholar
  141. Sazanov LA (2007) Respiratory complex I: mechanistic and structural insights provided by the crystal structure of the hydrophilic domain. Biochemistry 46:2275–2288PubMedGoogle Scholar
  142. Sazanov LA, Hinchliffe P (2006) Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus. Science 311:1430–1436PubMedGoogle Scholar
  143. Sazanov LA, Peak-Chew SY, Fearnley IM, Walker JE (2000) Resolution of the membrane domain of bovine complex I into subcomplexes: implications for the structural organization of the enzyme. Biochemistry 39:7229–7235PubMedGoogle Scholar
  144. Sazanov LA, Walker JE (2000) Cryo-electron crystallography of two sub-complexes of bovine complex I reveals the relationship between the membrane and peripheral arms. J Mol Biol 302:455–464PubMedGoogle Scholar
  145. Scacco S, Vergari R, Scarpulla RC, Technikova-Dobrova Z, Sardanelli A, Lambo R, Lorusso V, Papa S (2000) cAMP-dependent phosphorylation of the nuclear encoded 18-kDa (IP) subunit of respiratory complex I and activation of the complex in serum-starved mouse fibroblast cultures. J Biol Chem 275:17578–17582PubMedGoogle Scholar
  146. Schagger H (2002) Respiratory chain supercomplexes of mitochondria and bacteria. Biochim Biophys Acta 1555:154–159PubMedGoogle Scholar
  147. Schagger H, de Coo R, Bauer MF, Hofmann S, Godinot C, Brandt U (2004) Significance of respirasomes for the assembly/stability of human respiratory chain complex I. J Biol Chem 279:36349–36353PubMedGoogle Scholar
  148. Scheffler IE, Yadava N, Potluri P (2004) Molecular genetics of complex I-deficient Chinese hamster cell lines. Biochimica et Biophysica Acta (BBA)—Bioenergetics 1659:160–171Google Scholar
  149. Schilling B, Aggeler R, Schulenberg B, Murray J, Row RH, Capaldi RA, Gibson BW (2005) Mass spectrometric identification of a novel phosphorylation site in subunit NDUFA10 of bovine mitochondrial complex I. FEBS Lett 579:2485–2490PubMedGoogle Scholar
  150. Schneider R, Massow M, Lisowsky T, Weiss H (1995) Different respiratory-defective phenotypes of Neurospora crassa and Saccharomyces cerevisiae after inactivation of the gene encoding the mitochondrial acyl carrier protein. Curr Genet 29:10–17PubMedGoogle Scholar
  151. Schroda M (2006) RNA silencing in Chlamydomonas: mechanisms and tools. Curr Genet 49:69–84PubMedGoogle Scholar
  152. Schulenberg B, Aggeler R, Beechem JM, Capaldi RA, Patton WF (2003) Analysis of steady-state protein phosphorylation in mitochondria using a novel fluorescent phosphosensor dye. J Biol Chem 278:27251–27255PubMedGoogle Scholar
  153. Schuler F, Casida JE (2001) Functional coupling of PSST and ND1 subunits in NADH:ubiquinone oxidoreductase established by photoaffinity labeling. Biochim Biophys Acta 1506:79–87PubMedGoogle Scholar
  154. Schuler F, Yano T, Di Bernardo S, Yagi T, Yankovskaya V, Singer TP, Casida JE (1999) NADH-quinone oxidoreductase: PSST subunit couples electron transfer from iron–sulfur cluster N2 to quinone. Proc Natl Acad Sci USA 96:4149–4153PubMedGoogle Scholar
  155. Schulte U (2001) Biogenesis of respiratory complex I. J Bioenerg Biomembr 33:205–212PubMedGoogle Scholar
  156. Schulte U, Fecke W, Krull C, Nehls U, Schmiede A, Schneider R, Ohnishi T, Weiss H (1994) In vivo dissection of the mitochondrial respiratory NADH: ubiquinone oxidoreductase (complex I). Biochim Biophys Acta 1187:121–124PubMedGoogle Scholar
  157. Sellem CH, Lemaire C, Lorin S, Dujardin G, Sainsard-Chanet A (2005) Interaction between the oxa1 and rmp1 genes modulates respiratory complex assembly and life span in Podospora anserina. Genetics 169:1379–1389PubMedGoogle Scholar
  158. Seo T, Lee D, Shim YS, Angell JE, Chidambaram NV, Kalvakolanu DV, Choe J (2002) Viral interferon regulatory factor 1 of Kaposi’s Sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death. J Virol 76:8797–8807PubMedGoogle Scholar
  159. Skladal D, Halliday J, Thorburn DR (2003) Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 126:1905–1912PubMedGoogle Scholar
  160. Smeitink J, Sengers R, Trijbels F, van den Heuvel L (2001) Human NADH:ubiquinone oxidoreductase. J Bioenerg Biomembr 33:259–266PubMedGoogle Scholar
  161. Smith KS, Ferry JG (2000) Prokaryotic carbonic anhydrases. FEMS Microbiol Rev 24:335–366PubMedGoogle Scholar
  162. Steele DF, Butler CA, Fox TD (1996) Expression of a recoded nuclear gene inserted into yeast mitochondrial DNA is limited by mRNA-specific translational activation. Proc Natl Acad Sci USA 93:5253–5257PubMedGoogle Scholar
  163. Stephens JL, Lee SH, Paul KS, Englund PT (2007) Mitochondrial fatty acid synthesis in Trypanosoma brucei. J Biol Chem 282:4427–4436PubMedGoogle Scholar
  164. Stiburek L, Fornuskova D, Wenchich L, Pejznochova M, Hansikova H, Zeman J (2007) Knockdown of human Oxa1 l impairs the biogenesis of F1Fo-ATP synthase and NADH:ubiquinone oxidoreductase. J Mol Biol 374:506–516PubMedGoogle Scholar
  165. Sunderhaus S, Dudkina NV, Jansch L, Klodmann J, Heinemeyer J, Perales M, Zabaleta E, Boekema EJ, Braun HP (2006) Carbonic anhydrase subunits form a matrix-exposed domain attached to the membrane arm of mitochondrial complex I in plants. J Biol Chem 281:6482–6488PubMedGoogle Scholar
  166. Tocilescu MA, Fendel U, Zwicker K, Kerscher S, Brandt U (2007) Exploring the ubiquinone binding cavity of respiratory complex I. J Biol Chem 282:29514–29520PubMedGoogle Scholar
  167. Touraine B, Boutin J-P, Marion-Poll A, Briat J-F, Peltier G, Lobreaux S (2004) Nfu2: a scaffold protein required for [4Fe-4S] and ferredoxin iron–sulphur cluster assembly in Arabidopsis chloroplasts. Plant J 40:101–111PubMedGoogle Scholar
  168. Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA (2001) Respiratory chain complex I deficiency. Am J Med Genet 106:37–45PubMedGoogle Scholar
  169. Tripp BC, Bell CB 3rd, Cruz F, Krebs C, Ferry JG (2004) A role for iron in an ancient carbonic anhydrase. J Biol Chem 279:6683–6687PubMedGoogle Scholar
  170. Trounce IA, Pinkert CA (2007) Cybrid models of mtDNA disease and transmission, from cells to mice. Curr Top Dev Biol 77:157–183PubMedGoogle Scholar
  171. Tsang WY, Sayles LC, Grad LI, Pilgrim DB, Lemire BD (2001) Mitochondrial respiratory chain deficiency in Caenorhabditis elegans results in developmental arrest and increased life span. J Biol Chem 276:32240–32246PubMedGoogle Scholar
  172. Tsuneoka M, Teye K, Arima N, Soejima M, Otera H, Ohashi K, Koga Y, Fujita H, Shirouzu K, Kimura H, Koda Y (2005) A novel Myc-target gene, mimitin, that is involved in cell proliferation of esophageal squamous cell carcinoma. J Biol Chem 280:19977–19985PubMedGoogle Scholar
  173. Tuschen G, Sackmann U, Nehls U, Haiker H, Buse G, Weiss H (1990) Assembly of NADH: ubiquinone reductase (complex I) in Neurospora mitochondria. Independent pathways of nuclear-encoded and mitochondrially encoded subunits. J Mol Biol 213:845–857PubMedGoogle Scholar
  174. Ugalde C, Janssen RJ, van den Heuvel LP, Smeitink JA, Nijtmans LG (2004a) Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency. Hum Mol Genet 13:659–667PubMedGoogle Scholar
  175. Ugalde C, Vogel R, Huijbens R, Van Den Heuvel B, Smeitink J, Nijtmans L (2004b) Human mitochondrial complex I assembles through the combination of evolutionary conserved modules: a framework to interpret complex I deficiencies. Hum Mol Genet 13:2461–2472PubMedGoogle Scholar
  176. Vahsen N, Cande C, Briere JJ, Benit P, Joza N, Larochette N, Mastroberardino PG, Pequignot MO, Casares N, Lazar V, Feraud O, Debili N, Wissing S, Engelhardt S, Madeo F, Piacentini M, Penninger JM, Schagger H, Rustin P, Kroemer G (2004) AIF deficiency compromises oxidative phosphorylation. EMBO J 23:4679–4689PubMedGoogle Scholar
  177. van Lis R, Atteia A, Mendoza-Hernandez G, Gonzalez-Halphen D (2003) Identification of novel mitochondrial protein components of Chlamydomonas reinhardtii. A proteomic approach. Plant Physiol 132:318–330PubMedGoogle Scholar
  178. Videira A, Duarte M (2002) From NADH to ubiquinone in Neurospora mitochondria. Biochim Biophys Acta 1555:187–191PubMedGoogle Scholar
  179. Vogel R, Nijtmans L, Ugalde C, van den Heuvel L, Smeitink J (2004) Complex I assembly: a puzzling problem. Curr Opin Neurol 17:179–186PubMedGoogle Scholar
  180. Vogel RO, Dieteren CE, van den Heuvel LP, Willems PH, Smeitink JA, Koopman WJ, Nijtmans LG (2007a) Identification of mitochondrial complex I assembly intermediates by tracing tagged NDUFS3 demonstrates the entry point of mitochondrial subunits. J Biol Chem 282:7582–7590PubMedGoogle Scholar
  181. Vogel RO, Janssen RJ, Ugalde C, Grovenstein M, Huijbens RJ, Visch HJ, van den Heuvel LP, Willems PH, Zeviani M, Smeitink JA, Nijtmans LG (2005) Human mitochondrial complex I assembly is mediated by NDUFAF1. FEBS J 272:5317–5326PubMedGoogle Scholar
  182. Vogel RO, Janssen RJRJ, van den Brand MAM, Dieteren CEJ, Verkaart S, Koopman WJH, Willems PHGM, Pluk W, van den Heuvel LPWJ, Smeitink JAM, Nijtmans LGJ (2007b) Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly. Genes Dev 21:615–624PubMedGoogle Scholar
  183. Vogel RO, Smeitink JAM, Nijtmans LGJ (2007c) Human mitochondrial complex I assembly: a dynamic and versatile process. Biochimica et Biophysica Acta (BBA)—Bioenergetics 1767:1215–1227Google Scholar
  184. Vogel RO, van den Brand MAM, Rodenburg RJ, van den Heuvel LPWJ, Tsuneoka M, Smeitink JAM, Nijtmans LGJ (2007d) Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI deficient patients. Mol Genet Metab 91:176–182PubMedGoogle Scholar
  185. Yadava N, Scheffler IE (2004) Import and orientation of the MWFE protein in mitochondrial NADH-ubiquinone oxidoreductase. Mitochondrion 4:1–12PubMedGoogle Scholar
  186. Yagi T, Matsuno-Yagi A (2003) The proton-translocating NADH-quinone oxidoreductase in the respiratory chain: the secret unlocked. Biochemistry 42:2266–2274PubMedGoogle Scholar
  187. Yano T, Sled VD, Ohnishi T, Yagi T (1996) Expression and characterization of the flavoprotein subcomplex composed of 50-kDa (NQO1) and 25-kDa (NQO2) subunits of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans. J Biol Chem 271:5907–5913PubMedGoogle Scholar
  188. Zee JM, Glerum DM (2006) Defects in cytochrome oxidase assembly in humans: lessons from yeast. Biochem Cell Biol 84:859–869PubMedGoogle Scholar
  189. Zensen R, Husmann H, Schneider R, Peine T, Weiss H (1992) De novo synthesis and desaturation of fatty acids at the mitochondrial acyl-carrier protein, a subunit of NADH:ubiquinone oxidoreductase in Neurospora crassa. FEBS Lett 310:179–181PubMedGoogle Scholar
  190. Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, Poli V, Stark GR, Kalvakolanu DV (2003) The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. Proc Natl Acad Sci USA 100:9342–9347PubMedGoogle Scholar
  191. Zickermann V, Barquera B, Wikstrom 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 37:11792–11796PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Genetics of Microorganisms Laboratory, Department of Life SciencesUniversity of LiègeLiègeBelgium
  2. 2.Department of Plant Cellular and Molecular Biology and Department of Molecular and Cellular BiochemistryThe Ohio State UniversityColumbusUSA

Personalised recommendations