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NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase)
Symbols NDUFS1 ; CI-75Kd; CI-75k; PRO1304
External IDs OMIM157655 MGI2443241 HomoloGene3670 GeneCards: NDUFS1 Gene
EC number,
RNA expression pattern
PBB GE NDUFS1 203039 s at tn.png
More reference expression data
Species Human Mouse
Entrez 4719 227197
Ensembl ENSG00000023228 ENSMUSG00000025968
UniProt P28331 Q91VD9
RefSeq (mRNA) NM_001199981 NM_001160038
RefSeq (protein) NP_001186910 NP_001153510
Location (UCSC) Chr 2:
206.11 – 206.16 Mb
Chr 1:
63.14 – 63.18 Mb
PubMed search [1] [2]

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial is an enzyme that in humans is encoded by the NDUFS1 gene.[1][2]


The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized.[2]

Clinical significance[edit]

Mutations in the NDUFS1 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders.[3][4] Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible.[5] However, the majority of cases are caused by mutations in nuclear-encoded genes.[6][7] It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[8]


  1. ^ Chow W, Ragan I, Robinson BH (Nov 1991). "Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase". European Journal of Biochemistry / FEBS 201 (3): 547–50. doi:10.1111/j.1432-1033.1991.tb16313.x. PMID 1935949. 
  2. ^ a b "Entrez Gene: NDUFS1 NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase)". 
  3. ^ Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM, Kirk EP, Boneh A, Taylor RW, Dahl HH, Ryan MT, Thorburn DR (Sep 2004). "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–45. doi:10.1172/JCI20683. PMID 15372108. 
  4. ^ McFarland R, Kirby DM, Fowler KJ, Ohtake A, Ryan MT, Amor DJ, Fletcher JM, Dixon JW, Collins FA, Turnbull DM, Taylor RW, Thorburn DR (Jan 2004). "De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency". Annals of Neurology 55 (1): 58–64. doi:10.1002/ana.10787. PMID 14705112. 
  5. ^ Haack TB, Haberberger B, Frisch EM, Wieland T, Iuso A, Gorza M, Strecker V, Graf E, Mayr JA, Herberg U, Hennermann JB, Klopstock T, Kuhn KA, Ahting U, Sperl W, Wilichowski E, Hoffmann GF, Tesarova M, Hansikova H, Zeman J, Plecko B, Zeviani M, Wittig I, Strom TM, Schuelke M, Freisinger P, Meitinger T, Prokisch H (Apr 2012). "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing". Journal of Medical Genetics 49 (4): 277–83. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. 
  6. ^ 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". Human Mutation 15 (2): 123–34. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489. 
  7. ^ Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA (2001). "Respiratory chain complex I deficiency". American Journal of Medical Genetics 106 (1): 37–45. doi:10.1002/ajmg.1397. PMID 11579423. 
  8. ^ Robinson BH (May 1998). "Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect". Biochimica Et Biophysica Acta 1364 (2): 271–86. PMID 9593934. 

Further reading[edit]

  • Duncan AM, Chow W, Robinson BH (1992). "Localization of the human 75-kDal Fe-S protein of NADH-coenzyme Q reductase gene (NDUFS1) to 2q33----q34". Cytogenetics and Cell Genetics 60 (3-4): 212–3. doi:10.1159/000133340. PMID 1505218. 
  • Sumegi B, Srere PA (Dec 1984). "Complex I binds several mitochondrial NAD-coupled dehydrogenases". The Journal of Biological Chemistry 259 (24): 15040–5. PMID 6439716. 
  • Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA (Dec 1998). "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochemical and Biophysical Research Communications 253 (2): 415–22. doi:10.1006/bbrc.1998.9786. PMID 9878551. 
  • Bénit P, Chretien D, Kadhom N, de Lonlay-Debeney P, Cormier-Daire V, Cabral A, Peudenier S, Rustin P, Munnich A, Rötig A (Jun 2001). "Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency". American Journal of Human Genetics 68 (6): 1344–52. doi:10.1086/320603. PMC 1226121. PMID 11349233. 
  • Ricci JE, Muñoz-Pinedo C, Fitzgerald P, Bailly-Maitre B, Perkins GA, Yadava N, Scheffler IE, Ellisman MH, Green DR (Jun 2004). "Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain". Cell 117 (6): 773–86. doi:10.1016/j.cell.2004.05.008. PMID 15186778. 
  • Martín MA, Blázquez A, Gutierrez-Solana LG, Fernández-Moreira D, Briones P, Andreu AL, Garesse R, Campos Y, Arenas J (Apr 2005). "Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene". Archives of Neurology 62 (4): 659–61. doi:10.1001/archneur.62.4.659. PMID 15824269. 
  • Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  • Iuso A, Scacco S, Piccoli C, Bellomo F, Petruzzella V, Trentadue R, Minuto M, Ripoli M, Capitanio N, Zeviani M, Papa S (Apr 2006). "Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I". The Journal of Biological Chemistry 281 (15): 10374–80. doi:10.1074/jbc.M513387200. PMID 16478720. 
  • Piccoli C, Scacco S, Bellomo F, Signorile A, Iuso A, Boffoli D, Scrima R, Capitanio N, Papa S (Aug 2006). "cAMP controls oxygen metabolism in mammalian cells". FEBS Letters 580 (18): 4539–43. doi:10.1016/j.febslet.2006.06.085. PMID 16870178.