NDUFS4

NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase)
Identifiers
Symbols	NDUFS4; AQDQ; CI-18
External IDs	OMIM: 602694 MGI: 1343135 HomoloGene: 1866 GeneCards: NDUFS4 Gene
Gene Ontology Molecular function • NADH dehydrogenase (ubiquinone) activity • NADH dehydrogenase (ubiquinone) activity • oxidoreductase activity, acting on NADH or NADPH Cellular component • mitochondrion • mitochondrial inner membrane • mitochondrial respiratory chain complex I • mitochondrial respiratory chain complex I • membrane Biological process • regulation of protein phosphorylation • mitochondrial electron transport, NADH to ubiquinone • transport • brain development • cAMP-mediated signaling • respiratory electron transport chain • mitochondrial respiratory chain complex I assembly • cellular respiration • positive regulation of fibroblast proliferation • response to cAMP • reactive oxygen species metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4724	17993
Ensembl	ENSG00000164258	ENSMUSG00000021764
UniProt	O43181	Q923F9
RefSeq (mRNA)	NM_002495	NM_010887.2
RefSeq (protein)	NP_002486	NP_035017.2
Location (UCSC)	Chr 5: 52.86 – 52.98 Mb	Chr 13: 115.08 – 115.18 Mb
PubMed search	[1]	[2]

NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial also known as NADH-ubiquinone oxidoreductase 18 kDa subunit is an enzyme that in humans is encoded by the NDUFS4 gene.^[1][2][3]

Function

Complex I, or NADH:ubiquinone oxidoreductase, the first multisubunit enzyme complex of the mitochondrial respiratory chain chain, plays a vital role in cellular ATP production, the primary source of energy for many crucial processes in living cells. It removes electrons from NADH and passes them by a series of different protein-coupled redox centers to the electron acceptor ubiquinone. In well-coupled mitochondria, the electron flux leads to ATP generation via the building of a proton gradient across the inner membrane. Complex I is composed of at least 41 subunits, of which 7 are encoded by the mitochondrial genome (ND1-6, ND4L) and the remainder by nuclear genes.^[3][1]

References

1. ^ ^{a b} van den Heuvel L, Ruitenbeek W, Smeets R, Gelman-Kohan Z, Elpeleg O, Loeffen J, Trijbels F, Mariman E, de Bruijn D, Smeitink J (Apr 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 Hum Genet 62 (2): 262–8. doi:10.1086/301716. PMC 1376892. PMID 9463323. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1376892. 
2. ^ Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenet Cell Genet 82 (1–2): 115–9. doi:10.1159/000015082. PMID 9763677. 
3. ^ ^{a b} "Entrez Gene: NDUFS4 NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4724. 

Further reading

• Papa S, Sardanelli AM, Scacco S, et al. (2003). "The NADH: ubiquinone oxidoreductase (complex I) of the mammalian respiratory chain and the cAMP cascade". J. Bioenerg. Biomembr. 34 (1): 1–10. doi:10.1023/A:1013863018115. PMID 11860175. 
• Pilkington SJ, Skehel JM, Gennis RB, Walker JE (1991). "Relationship between mitochondrial NADH-ubiquinone reductase and a bacterial NAD-reducing hydrogenase". Biochemistry 30 (8): 2166–75. doi:10.1021/bi00222a021. PMID 1900194. 
• Loeffen JL, Triepels RH, van den Heuvel LP, et al. (1999). "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochem. Biophys. Res. Commun. 253 (2): 415–22. doi:10.1006/bbrc.1998.9786. PMID 9878551. 
• Triepels RH, Hanson BJ, van den Heuvel LP, et al. (2001). "Human complex I defects can be resolved by monoclonal antibody analysis into distinct subunit assembly patterns". J. Biol. Chem. 276 (12): 8892–7. doi:10.1074/jbc.M009903200. PMID 11112787. 
• Papa S, Scacco S, Sardanelli AM, et al. (2001). "Mutation in the NDUFS4 gene of complex I abolishes cAMP-dependent activation of the complex in a child with fatal neurological syndrome". FEBS Lett. 489 (2–3): 259–62. doi:10.1016/S0014-5793(00)02334-6. PMID 11165261. 
• Petruzzella V, Vergari R, Puzziferri I, et al. (2001). "A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome". Hum. Mol. Genet. 10 (5): 529–35. doi:10.1093/hmg/10.5.529. PMID 11181577. 
• Roef MJ, Reijngoud DJ, Jeneson JA, et al. (2002). "Resting oxygen consumption and in vivo ADP are increased in myopathy due to complex I deficiency". Neurology 58 (7): 1088–93. PMID 11940698. 
• Lee BH, Lee H, Xiong L, Zhu JK (2002). "A mitochondrial complex I defect impairs cold-regulated nuclear gene expression". Plant Cell 14 (6): 1235–51. doi:10.1105/tpc.010433. PMC 150777. PMID 12084824. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=150777. 
• Papa S (2002). "The NDUFS4 nuclear gene of complex I of mitochondria and the cAMP cascade". Biochim. Biophys. Acta 1555 (1–3): 147–53. doi:10.1016/S0005-2728(02)00270-0. PMID 12206907. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Bénit P, Steffann J, Lebon S, et al. (2003). "Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome". Hum. Genet. 112 (5–6): 563–6. doi:10.1007/s00439-002-0884-2. PMID 12616398. 
• Scacco S, Petruzzella V, Budde S, et al. (2004). "Pathological mutations of the human NDUFS4 gene of the 18-kDa (AQDQ) subunit of complex I affect the expression of the protein and the assembly and function of the complex". J. Biol. Chem. 278 (45): 44161–7. doi:10.1074/jbc.M307615200. PMID 12944388. 
• Budde SM, van den Heuvel LP, Smeets RJ, et al. (2004). "Clinical heterogeneity in patients with mutations in the NDUFS4 gene of mitochondrial complex I". J. Inherit. Metab. Dis. 26 (8): 813–5. doi:10.1023/B:BOLI.0000010003.14113.af. PMID 14765537. 
• Papa S, Petruzzella V, Scacco S, et al. (2004). "Respiratory complex I in brain development and genetic disease". Neurochem. Res. 29 (3): 547–60. doi:10.1023/B:NERE.0000014825.42365.16. PMID 15038602. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Petruzzella V, Panelli D, Torraco A, et al. (2005). "Mutations in the NDUFS4 gene of mitochondrial complex I alter stability of the splice variants". FEBS Lett. 579 (17): 3770–6. doi:10.1016/j.febslet.2005.05.035. PMID 15975579. 
• Tao WA, Wollscheid B, O'Brien R, et al. (2005). "Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry". Nat. Methods 2 (8): 591–8. doi:10.1038/nmeth776. PMID 16094384.