electron transport complex i


Summary: A flavoprotein and iron sulfur-containing oxidoreductase complex that catalyzes the conversion of UBIQUINONE to ubiquinol. In MITOCHONDRIA the complex also couples its reaction to the transport of PROTONS across the internal mitochondrial membrane. The NADH DEHYDROGENASE component of the complex can be isolated and is listed as EC

Top Publications

  1. Zurita Rendón O, Shoubridge E. Early complex I assembly defects result in rapid turnover of the ND1 subunit. Hum Mol Genet. 2012;21:3815-24 pubmed publisher
    ..These data suggest that the four early CI assembly factors have non-redundant functions in the assembly of a module that docks and stabilizes newly synthesized ND1, nucleating assembly of the holoenzyme. ..
  2. Chouchani E, Methner C, Nadtochiy S, Logan A, Pell V, Ding S, et al. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med. 2013;19:753-9 pubmed publisher
  3. Quintana A, Zanella S, Koch H, Kruse S, Lee D, RAMIREZ J, et al. Fatal breathing dysfunction in a mouse model of Leigh syndrome. J Clin Invest. 2012;122:2359-68 pubmed publisher
    ..These data demonstrate that mitochondrial dysfunction within the VN results in aberrant regulation of respiration and contributes to the lethality of Ndufs4-knockout mice. ..
  4. Narayanan M, Gabrieli D, Leung S, Elguindy M, Glaser C, Saju N, et al. Semiquinone and cluster N6 signals in His-tagged proton-translocating NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli. J Biol Chem. 2013;288:14310-9 pubmed publisher
    ..85 milliwatts. The semiquinone signal(s) decreased by 60% when with asimicin, a potent complex I inhibitor. The functional role of semiquinone and the EPR assignment of clusters N6a/N6b are discussed. ..
  5. Babot M, Galkin A. Molecular mechanism and physiological role of active-deactive transition of mitochondrial complex I. Biochem Soc Trans. 2013;41:1325-30 pubmed publisher
    ..The nature of thiol modification defines deactivation reversibility, the reactivation timescale, the status of mitochondrial bioenergetics and therefore the degree of recovery of the ischaemic tissues after reoxygenation. ..
  6. Tucker E, Mimaki M, Compton A, McKenzie M, Ryan M, Thorburn D. Next-generation sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation. Hum Mutat. 2012;33:411-8 pubmed publisher
    ..It is important that locus-specific databases contain accurate information on pathogenic variation. NGS data, therefore, require rigorous experimental follow-up to confirm mutation pathogenicity. ..
  7. Baradaran R, Berrisford J, Minhas G, Sazanov L. Crystal structure of the entire respiratory complex I. Nature. 2013;494:443-8 pubmed publisher
  8. Ciano M, Fuszard M, Heide H, Botting C, Galkin A. Conformation-specific crosslinking of mitochondrial complex I. FEBS Lett. 2013;587:867-72 pubmed publisher
  9. Santidrian A, Matsuno Yagi A, Ritland M, Seo B, LeBoeuf S, Gay L, et al. Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest. 2013;123:1068-81 pubmed publisher

More Information


  1. Clerc P, Polster B. Investigation of mitochondrial dysfunction by sequential microplate-based respiration measurements from intact and permeabilized neurons. PLoS ONE. 2012;7:e34465 pubmed publisher
  2. Pätsi J, Maliniemi P, Pakanen S, Hinttala R, Uusimaa J, Majamaa K, et al. LHON/MELAS overlap mutation in ND1 subunit of mitochondrial complex I affects ubiquinone binding as revealed by modeling in Escherichia coli NDH-1. Biochim Biophys Acta. 2012;1817:312-8 pubmed publisher
    ..In all, m.3376G>A perturbs ubiquinone binding, a phenomenon found in LHON, and decreases the activity of fully assembled complex I as in MELAS. ..
  3. Shiraishi Y, Murai M, Sakiyama N, Ifuku K, Miyoshi H. Fenpyroximate binds to the interface between PSST and 49 kDa subunits in mitochondrial NADH-ubiquinone oxidoreductase. Biochemistry. 2012;51:1953-63 pubmed publisher
    ..This study answers a critical question relating to complex I...
  4. Moreno Lastres D, Fontanesi F, Garcia Consuegra I, Martin M, Arenas J, Barrientos A, et al. Mitochondrial complex I plays an essential role in human respirasome assembly. Cell Metab. 2012;15:324-35 pubmed publisher
  5. Stroud D, Formosa L, Wijeyeratne X, Nguyen T, Ryan M. Gene knockout using transcription activator-like effector nucleases (TALENs) reveals that human NDUFA9 protein is essential for stabilizing the junction between membrane and matrix arms of complex I. J Biol Chem. 2013;288:1685-90 pubmed publisher
    ..We conclude that NDUFA9 is involved in stabilizing the junction between membrane and matrix arms of complex I, a late assembly step critical for complex I biogenesis and activity. ..
  6. Li B, Chauvin C, De Paulis D, De Oliveira F, Gharib A, Vial G, et al. Inhibition of complex I regulates the mitochondrial permeability transition through a phosphate-sensitive inhibitory site masked by cyclophilin D. Biochim Biophys Acta. 2012;1817:1628-34 pubmed publisher
  7. Sanz M, Sanchez Martin C, Detaille D, Vial G, Rigoulet M, El Mir M, et al. Acute mitochondrial actions of glitazones on the liver: a crucial parameter for their antidiabetic properties. Cell Physiol Biochem. 2011;28:899-910 pubmed publisher
    ..This new finding could positively contribute to their anti-diabetic properties. ..
  8. Hatle K, Gummadidala P, Navasa N, Bernardo E, Dodge J, Silverstrim B, et al. MCJ/DnaJC15, an endogenous mitochondrial repressor of the respiratory chain that controls metabolic alterations. Mol Cell Biol. 2013;33:2302-14 pubmed publisher
    ..Impaired expression or loss of MCJ expression may therefore result in a "rapid" metabolism that mitigates the consequences of metabolic disorders. ..
  9. Wikstrom M, Hummer G. Stoichiometry of proton translocation by respiratory complex I and its mechanistic implications. Proc Natl Acad Sci U S A. 2012;109:4431-6 pubmed publisher
    ..In a rough mechanistic model, we suggest a concerted proton translocation mechanism in the three homologous and tightly packed antiporter-like subunits L, M, and N of the proton-translocating membrane domain of complex I...
  10. Kevelam S, Rodenburg R, Wolf N, Ferreira P, Lunsing R, Nijtmans L, et al. NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern. Neurology. 2013;80:1577-83 pubmed publisher
  11. Hirst J. Mitochondrial complex I. Annu Rev Biochem. 2013;82:551-75 pubmed publisher
  12. Cho J, Hur J, Graniel J, Benzer S, Walker D. Expression of yeast NDI1 rescues a Drosophila complex I assembly defect. PLoS ONE. 2012;7:e50644 pubmed publisher
    ..Our work shows that CG7598/dCIA30 is a functional homolog of Ndufaf1 and adds to the accumulating evidence that transgenic NDI1 expression is a viable therapy for disorders arising from complex I deficiency. ..
  13. Pagniez Mammeri H, Loublier S, Legrand A, Benit P, Rustin P, Slama A. Mitochondrial complex I deficiency of nuclear origin I. Structural genes. Mol Genet Metab. 2012;105:163-72 pubmed publisher
    ..The majority of the pathogenic mutations are private and the genotype-phenotype correlation is inconsistent in the rare recurrent mutations. ..
  14. Verkhovsky M, Bloch D, Verkhovskaya M. Tightly-bound ubiquinone in the Escherichia coli respiratory complex I. Biochim Biophys Acta. 2012;1817:1550-6 pubmed publisher
    ..Such perturbed redox properties of ubiquinone indicate that it is tightly bound to the enzyme's hydrophobic core. The possibility of two ubiquinone-binding sites in Complex I is discussed. ..
  15. Vilain S, Esposito G, Haddad D, Schaap O, Dobreva M, Vos M, et al. The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants. PLoS Genet. 2012;8:e1002456 pubmed publisher
  16. Nesbitt V, Morrison P, Crushell E, Donnelly D, Alston C, He L, et al. The clinical spectrum of the m.10191T>C mutation in complex I-deficient Leigh syndrome. Dev Med Child Neurol. 2012;54:500-6 pubmed publisher
  17. Bridges H, Bill E, Hirst J. Mössbauer spectroscopy on respiratory complex I: the iron-sulfur cluster ensemble in the NADH-reduced enzyme is partially oxidized. Biochemistry. 2012;51:149-58 pubmed publisher
    ..The implications for intramolecular electron transfer along the extended chain of cofactors in complex I are discussed...
  18. Zhu Q, Dugardeyn J, Zhang C, Takenaka M, Kuhn K, Craddock C, et al. SLO2, a mitochondrial pentatricopeptide repeat protein affecting several RNA editing sites, is required for energy metabolism. Plant J. 2012;71:836-49 pubmed publisher
    ..We propose that SLO2 is required for carbon energy balance in Arabidopsis by maintaining the abundance and/or activity of complexes I, III, and IV of the mitochondrial electron transport chain. ..
  19. Roberts P, Hirst J. The deactive form of respiratory complex I from mammalian mitochondria is a Na+/H+ antiporter. J Biol Chem. 2012;287:34743-51 pubmed publisher
    ..The deactive state of complex I is formed during hypoxia, when respiratory chain turnover is slowed, and may contribute to determining the outcome of ischemia-reperfusion injury. ..
  20. Nouws J, Nijtmans L, Smeitink J, Vogel R. Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options. Brain. 2012;135:12-22 pubmed publisher
    ..In this review, we will address whether the functions of these chaperones point towards a general molecular mechanism of disease and whether this enables us to design a treatment for complex I deficiency. ..
  21. van den Bosch B, Gerards M, Sluiter W, Stegmann A, Jongen E, Hellebrekers D, et al. Defective NDUFA9 as a novel cause of neonatally fatal complex I disease. J Med Genet. 2012;49:10-5 pubmed publisher
  22. Efremov R, Sazanov L. Respiratory complex I: 'steam engine' of the cell?. Curr Opin Struct Biol. 2011;21:532-40 pubmed publisher
    ..The proposed mechanism of coupling between electron transfer and proton translocation involves long-range conformational changes, coordinated in part by a long ?-helix, akin to the coupling rod of a steam engine. ..
  23. Bridges H, Birrell J, Hirst J. The mitochondrial-encoded subunits of respiratory complex I (NADH:ubiquinone oxidoreductase): identifying residues important in mechanism and disease. Biochem Soc Trans. 2011;39:799-806 pubmed publisher
    ..Thus we aim to identify and discuss residues in the ND subunits of mammalian complex I which are important in catalysis and for maintaining the enzyme's structural and functional integrity. ..
  24. Valsecchi F, Koopman W, Manjeri G, Rodenburg R, Smeitink J, Willems P. Complex I disorders: causes, mechanisms, and development of treatment strategies at the cellular level. Dev Disabil Res Rev. 2010;16:175-82 pubmed publisher
    ..There are currently no rational treatment strategies. Here, we present an overview of the genetic origins and cellular consequences of this deficiency and discuss how these insights might aid future development of treatment strategies. ..
  25. Batista A, Fernandes A, Louro R, Steuber J, Pereira M. Energy conservation by Rhodothermus marinus respiratory complex I. Biochim Biophys Acta. 2010;1797:509-15 pubmed publisher
  26. Shen L, Wei J, Chen T, He J, Qu J, He X, et al. Evaluating mitochondrial DNA in patients with breast cancer and benign breast disease. J Cancer Res Clin Oncol. 2011;137:669-75 pubmed publisher
    ..Finally, we found haplogroup M has an increased risk of breast cancer compared with haplogroup N. mtDNA mutation may play a role in early stage of tumorigenesis, and mitochondrial haplogroup can also modulate breast cancer occurrence...
  27. Hayashi T, Stuchebrukhov A. Electron tunneling in respiratory complex I. Proc Natl Acad Sci U S A. 2010;107:19157-62 pubmed publisher
    ..The unusual electronic structure properties of Fe(4)S(4) clusters in complex I explain their remarkable efficiency of electron transfer. ..
  28. Birrell J, Hirst J. Truncation of subunit ND2 disrupts the threefold symmetry of the antiporter-like subunits in complex I from higher metazoans. FEBS Lett. 2010;584:4247-52 pubmed publisher
    ..Nature 465, 441-447). Here, we show that in higher metazoans the threefold symmetry is broken by the loss of three helices from subunit ND2; possible implications for the mechanism of proton translocation are discussed...
  29. Medvedev E, Couch V, Stuchebrukhov A. Determination of the intrinsic redox potentials of FeS centers of respiratory complex I from experimental titration curves. Biochim Biophys Acta. 2010;1797:1665-71 pubmed publisher
  30. Koprivova A, des Francs Small C, Calder G, Mugford S, Tanz S, Lee B, et al. Identification of a pentatricopeptide repeat protein implicated in splicing of intron 1 of mitochondrial nad7 transcripts. J Biol Chem. 2010;285:32192-9 pubmed publisher
    ..The same phenotype was observed with other mutants affected in function of Complex I, thus reinforcing the importance of Complex I function for cellular redox homeostasis. ..
  31. Kann O, Huchzermeyer C, Kovacs R, Wirtz S, Schuelke M. Gamma oscillations in the hippocampus require high complex I gene expression and strong functional performance of mitochondria. Brain. 2011;134:345-58 pubmed publisher
    ..Our study helps to explain the exceptional vulnerability of complex brain functions in ischaemia as well as in neurodegenerative and psychiatric disorders that are associated with mitochondrial dysfunction. ..
  32. Calvo S, Tucker E, Compton A, Kirby D, Crawford G, Burtt N, et al. High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat Genet. 2010;42:851-8 pubmed publisher
    ..Our study illustrates how large-scale sequencing, coupled with functional prediction and experimental validation, can be used to identify causal mutations in individual cases. ..
  33. Birrell J, King M, Hirst J. A ternary mechanism for NADH oxidation by positively charged electron acceptors, catalyzed at the flavin site in respiratory complex I. FEBS Lett. 2011;585:2318-22 pubmed publisher
    ..Our mechanism for paraquat reduction defines a new mechanism for superoxide production by complex I (by redox cycling); in contrast to direct O(2) reduction the rate is stimulated, not inhibited, by high NADH concentrations. ..
  34. Pryde K, Hirst J. Superoxide is produced by the reduced flavin in mitochondrial complex I: a single, unified mechanism that applies during both forward and reverse electron transfer. J Biol Chem. 2011;286:18056-65 pubmed publisher
    ..It establishes a route to understanding causative connections between the enzyme and its pathological effects and to developing rational strategies for addressing them. ..
  35. Brandt U. A two-state stabilization-change mechanism for proton-pumping complex I. Biochim Biophys Acta. 2011;1807:1364-9 pubmed publisher
    ..This article is part of a Special Issue entitled Allosteric cooperativity in respiratory proteins. ..
  36. Mimaki M, Wang X, McKenzie M, Thorburn D, Ryan M. Understanding mitochondrial complex I assembly in health and disease. Biochim Biophys Acta. 2012;1817:851-62 pubmed publisher
    ..This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. ..
  37. Bannwarth S, Abbassi M, Valéro R, Fragaki K, Dubois N, Vialettes B, et al. A novel unstable mutation in mitochondrial DNA responsible for maternally inherited diabetes and deafness. Diabetes Care. 2011;34:2591-3 pubmed publisher
    ..The m.3243A>G mutation in mitochondrial DNA (mtDNA) is responsible for maternally inherited diabetes and deafness (MIDD). Other mtDNA mutations are extremely rare...
  38. Hirst J. Why does mitochondrial complex I have so many subunits?. Biochem J. 2011;437:e1-3 pubmed publisher
    ..have provided new evidence to suggest that the supernumerary subunits are important for enzyme stability. This commentary aims to put this suggestion into context. ..
  39. Roessler M, King M, Robinson A, Armstrong F, Harmer J, Hirst J. Direct assignment of EPR spectra to structurally defined iron-sulfur clusters in complex I by double electron-electron resonance. Proc Natl Acad Sci U S A. 2010;107:1930-5 pubmed publisher
    ..The implications of our assignment for the mechanisms of electron transfer and energy transduction by complex I are discussed. ..
  40. Dudkina N, Kudryashev M, Stahlberg H, Boekema E. Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography. Proc Natl Acad Sci U S A. 2011;108:15196-200 pubmed publisher
    ..Modeling indicates a loose interaction between the three complexes and provides evidence that lipids are gluing them at the interfaces. ..
  41. Kelly Aubert M, Trudel S, Fritsch J, Nguyen Khoa T, Baudouin Legros M, Moriceau S, et al. GSH monoethyl ester rescues mitochondrial defects in cystic fibrosis models. Hum Mol Genet. 2011;20:2745-59 pubmed publisher
    ..These studies provide evidence for a critical role of a mtGSH defect in mitochondrial dysfunction and abnormal IL-8 secretion in CF cells and reveal the therapeutic potential of mitochondria-targeted antioxidants in CF. ..
  42. Birungi M, Folea M, Battchikova N, Xu M, Mi H, Ogawa T, et al. Possibilities of subunit localization with fluorescent protein tags and electron microscopy examplified by a cyanobacterial NDH-1 study. Biochim Biophys Acta. 2010;1797:1681-6 pubmed publisher
  43. Althoff T, Mills D, Popot J, Kuhlbrandt W. Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J. 2011;30:4652-64 pubmed publisher
    ..The arrangement of respiratory chain complexes suggests two possible pathways for efficient electron transfer through the supercomplex, of which the shorter branch through the complex III monomer proximal to complex I may be preferred. ..
  44. Yang Y, Yamashita T, Nakamaru Ogiso E, Hashimoto T, Murai M, Igarashi J, et al. Reaction mechanism of single subunit NADH-ubiquinone oxidoreductase (Ndi1) from Saccharomyces cerevisiae: evidence for a ternary complex mechanism. J Biol Chem. 2011;286:9287-97 pubmed publisher
    ..Taken together, unlike other NAD(P)H-UQ oxidoreductases, the Ndi1 reaction proceeds through a ternary complex (not a ping-pong) mechanism. The bound UQ keeps oxygen away from the reduced flavin. ..
  45. McKenzie M, Ryan M. Assembly factors of human mitochondrial complex I and their defects in disease. IUBMB Life. 2010;62:497-502 pubmed publisher
    ..Defects in assembly factors which disrupt complex I assembly and contribute to human disease pathogenesis will also be discussed. ..
  46. Papa S, Rasmo D, Technikova Dobrova Z, Panelli D, Signorile A, Scacco S, et al. Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases. FEBS Lett. 2012;586:568-77 pubmed publisher
    ..Complex I dysfunction has, indeed, been found, to be associated with several human diseases. Knowledge of the pathogenetic mechanisms of these diseases can help to develop new therapeutic strategies. ..
  47. Carilla Latorre S, Gallardo M, Annesley S, Calvo Garrido J, Grana O, Accari S, et al. MidA is a putative methyltransferase that is required for mitochondrial complex I function. J Cell Sci. 2010;123:1674-83 pubmed publisher
    ..We found that these aspects of the phenotype are mediated by a chronic activation of AMPK, revealing a possible role of AMPK signaling in complex I cytopathology. ..
  48. Sanz A, Soikkeli M, Portero Otin M, Wilson A, Kemppainen E, McIlroy G, et al. Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction. Proc Natl Acad Sci U S A. 2010;107:9105-10 pubmed publisher
    ..Our results support a central role of mitochondrial oxidative phosphorylation complex I in influencing longevity via oxidative stress, independently of pathways connected to nutrition and growth signaling. ..
  49. Greene J, Dingledine R, Greenamyre J. Neuron-selective changes in RNA transcripts related to energy metabolism in toxic models of parkinsonism in rodents. Neurobiol Dis. 2010;38:476-81 pubmed publisher
  50. Friedrich T, Hellwig P. Redox-induced conformational changes within the Escherichia coli NADH ubiquinone oxidoreductase (complex I): an analysis by mutagenesis and FT-IR spectroscopy. Biochim Biophys Acta. 2010;1797:659-63 pubmed publisher
    ..This residue is located in the vicinity of the cluster N2. Re-evaluating these previous data we here discuss a mechanism, by which the redox reaction of N2 induces conformational changes possibly leading to proton translocation. ..
  51. Kuhn K, Carrie C, Giraud E, Wang Y, Meyer E, Narsai R, et al. The RCC1 family protein RUG3 is required for splicing of nad2 and complex I biogenesis in mitochondria of Arabidopsis thaliana. Plant J. 2011;67:1067-80 pubmed publisher
    ..This observation is consistent with global transcript changes indicating enhanced mitochondrial biogenesis in the rug3 mutant in response to the complex I defect. ..
  52. Batista A, Pereira M. Sodium influence on energy transduction by complexes I from Escherichia coli and Paracoccus denitrificans. Biochim Biophys Acta. 2011;1807:286-92 pubmed publisher
    ..marinus enzyme. Nevertheless, the Na(+)/H(+) antiport activity seems not to be a general property of complex I, which may be correlated with the metabolic characteristics of the organisms...
  53. García Ruiz I, Fernandez Moreira D, Solís Muñoz P, Rodríguez Juan C, Díaz Sanjuán T, Muñoz Yagüe T, et al. Mitochondrial complex I subunits are decreased in murine nonalcoholic fatty liver disease: implication of peroxynitrite. J Proteome Res. 2010;9:2450-9 pubmed publisher
    ..Exposure of mitochondrial proteins from normal mice to peroxynitrite reproduced the proteomic abnormalities present in ob/ob mice. ..