NDUFS2

NDUFS2
Identifiers
Aliases NDUFS2, CI-49, NADH:ubiquinone oxidoreductase core subunit S2
External IDs MGI: 2385112 HomoloGene: 56659 GeneCards: NDUFS2
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

4720

226646

Ensembl

ENSG00000158864

ENSMUSG00000013593

UniProt

O75306

Q91WD5

RefSeq (mRNA)

NM_001166159
NM_004550

NM_153064

RefSeq (protein)

NP_001159631.1
NP_004541.1

NP_694704.1

Location (UCSC) Chr 1: 161.2 – 161.21 Mb Chr 1: 171.23 – 171.25 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an enzyme that in humans is encoded by the NDUFS2 gene.[3][4][5]

Function

Mitochondrial complex I is the first multimeric complex of the respiratory chain that catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mammalian mitochondrial complex I is an assembly of at least 43 different subunits. Seven of the subunits are encoded by the mitochondrial genome; the remainder are the products of nuclear genes. The iron-sulfur protein (IP) fraction of complex I is made up of 7 subunits, including NDUFS2.[5]

Clinical significance

Mutations in the NDUFS2 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.[6][7] 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.[8] However, the majority of cases are caused by mutations in nuclear-encoded genes.[9][10] 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.[11]

See also

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Fearnley IM, Finel M, Skehel JM, Walker JE (Sep 1991). "NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits". The Biochemical Journal. 278. 278 (3): 821–9. doi:10.1042/bj2780821. PMC 1151420Freely accessible. PMID 1832859.
  4. ↑ Procaccio V, de Sury R, Martinez P, Depetris D, Rabilloud T, Soularue P, Lunardi J, Issartel J (Jun 1998). "Mapping to 1q23 of the human gene (NDUFS2) encoding the 49-kDa subunit of the mitochondrial respiratory Complex I and immunodetection of the mature protein in mitochondria". Mammalian Genome. 9 (6): 482–4. doi:10.1007/s003359900803. PMID 9585441.
  5. 1 2 "Entrez Gene: NDUFS2 NADH dehydrogenase (ubiquinone) Fe-S protein 2, 49kDa (NADH-coenzyme Q reductase)".
  6. ↑ 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. PMC 516258Freely accessible. PMID 15372108.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934.

Further reading

  • Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
  • Loeffen J, van den Heuvel L, Smeets R, Triepels R, Sengers R, Trijbels F, Smeitink J (Jun 1998). "cDNA sequence and chromosomal localization of the remaining three human nuclear encoded iron sulphur protein (IP) subunits of complex I: the human IP fraction is completed". Biochemical and Biophysical Research Communications. 247 (3): 751–8. doi:10.1006/bbrc.1998.8882. PMID 9647766. 
  • 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. 
  • Triepels RH, Hanson BJ, van den Heuvel LP, Sundell L, Marusich MF, Smeitink JA, Capaldi RA (Mar 2001). "Human complex I defects can be resolved by monoclonal antibody analysis into distinct subunit assembly patterns". The Journal of Biological Chemistry. 276 (12): 8892–7. doi:10.1074/jbc.M009903200. PMID 11112787. 
  • Loeffen J, Elpeleg O, Smeitink J, Smeets R, Stöckler-Ipsiroglu S, Mandel H, Sengers R, Trijbels F, van den Heuvel L (Feb 2001). "Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and encephalomyopathy". Annals of Neurology. 49 (2): 195–201. doi:10.1002/1531-8249(20010201)49:2<195::AID-ANA39>3.0.CO;2-M. PMID 11220739. 
  • Murray J, Taylor SW, Zhang B, Ghosh SS, Capaldi RA (Sep 2003). "Oxidative damage to mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass spectrometry". The Journal of Biological Chemistry. 278 (39): 37223–30. doi:10.1074/jbc.M305694200. PMID 12857734. 
  • Ugalde C, Janssen RJ, van den Heuvel LP, Smeitink JA, Nijtmans LG (Mar 2004). "Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency". Human Molecular Genetics. 13 (6): 659–67. doi:10.1093/hmg/ddh071. PMID 14749350. 
  • Bourges I, Ramus C, Mousson de Camaret B, Beugnot R, Remacle C, Cardol P, Hofhaus G, Issartel JP (Nov 2004). "Structural organization of mitochondrial human complex I: role of the ND4 and ND5 mitochondria-encoded subunits and interaction with prohibitin". The Biochemical Journal. 383 (Pt. 3): 491–9. doi:10.1042/BJ20040256. PMC 1133742Freely accessible. PMID 15250827. 
  • Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (Mar 2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis. 191 (1): 63–72. doi:10.1016/j.atherosclerosis.2006.05.032. PMID 16806233. 
  • Vogel RO, Dieteren CE, van den Heuvel LP, Willems PH, Smeitink JA, Koopman WJ, Nijtmans LG (Mar 2007). "Identification of mitochondrial complex I assembly intermediates by tracing tagged NDUFS3 demonstrates the entry point of mitochondrial subunits". The Journal of Biological Chemistry. 282 (10): 7582–90. doi:10.1074/jbc.M609410200. PMID 17209039. 


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