NDUFV1

NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial (NDUFV1) is an enzyme that in humans is encoded by the NDUFV1 gene.[5] The NDUFV1 gene encodes the 51-kD subunit of complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain. Defects in complex I are a common cause of mitochondrial dysfunction. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome.[6]

NDUFV1
Identifiers
AliasesNDUFV1, CI-51K, CI51KD, UQOR1, NADH:ubiquinone oxidoreductase core subunit V1, MC1DN4
External IDsOMIM: 161015 MGI: 107851 HomoloGene: 5151 GeneCards: NDUFV1
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q13.2Start67,605,653 bp[1]
End67,612,554 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

4723

17995

Ensembl

ENSG00000167792

ENSMUSG00000037916

UniProt

P49821

Q91YT0

RefSeq (mRNA)

NM_007103
NM_001166102

NM_133666

RefSeq (protein)

NP_001159574
NP_009034

NP_598427

Location (UCSC)Chr 11: 67.61 – 67.61 MbChr 19: 4.01 – 4.01 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

NDUFV1 is located on the q arm of chromosome 11 in position 13.2 and has 10 exons.[6] The NDUFV1 gene produces a 50.8 kDa protein composed of 464 amino acids.[7][8] NDUFV1, the protein encoded by this gene, is a member of the complex I 51 kDa subunit family. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-binding sites.[6] It also contains a transit peptide domain and is composed of 6 turns, 14 beta strands, and 19 alpha helixes.[9][10]

Function

Complex I is composed of 45 different subunits. NDUFV1 is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.[11] NDUFV1 is an oxidoreductase and core subunit of complex I that is thought to be required for assembly and catalysis. It is a peripheral membrane protein located on the matrix side of the mitochondrion inner membrane.[9][10]

Catalytic Activity

NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out).

NADH + acceptor = NAD+ + reduced acceptor.[9][10]

Clinical significance

Mutations in the NDUFV1 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.[12][13] 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.[14] However, the majority of cases are caused by mutations in nuclear-encoded genes.[15][16] 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.[17] Clinical manifestations can include lactic acidosis, cerebral degeneration, ophthalmoplegia, ataxia, spasticity, and dystonia resulting from mutations in NDUFV1.[18][19]

Interactions

NDUFV1 has been shown to have 103 binary protein-protein interactions including 97 co-complex interactions. NDUFV1 appears to interact with EWSR1, CREB1, NCOR1, and VDAC1.[20]

References
  1. GRCh38: Ensembl release 89: ENSG00000167792 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000037916 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Spencer SR, Taylor JB, Cowell IG, Xia CL, Pemble SE, Ketterer B (December 1992). "The human mitochondrial NADH: ubiquinone oxidoreductase 51-kDa subunit maps adjacent to the glutathione S-transferase P1-1 gene on chromosome 11q13". Genomics. 14 (4): 1116–8. doi:10.1016/S0888-7543(05)80144-2. PMID 1478657.
  6. "Entrez Gene: NDUFV1 NADH dehydrogenase (ubiquinone) flavoprotein 1, 51kDa". This article incorporates text from this source, which is in the public domain.
  7. Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-27.
  8. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  9. "NDUFV1 - NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial precursor - Homo sapiens (Human) - NDUFV1 gene & protein". www.uniprot.org. Retrieved 2018-08-27. This article incorporates text available under the CC BY 4.0 license.
  10. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  11. Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, Ghosh SS, Capaldi RA (April 2003). "The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification". The Journal of Biological Chemistry. 278 (16): 13619–22. doi:10.1074/jbc.C300064200. PMID 12611891.
  12. Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM, Kirk EP, Boneh A, Taylor RW, Dahl HH, Ryan MT, Thorburn DR (September 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 516258. PMID 15372108.
  13. McFarland R, Kirby DM, Fowler KJ, Ohtake A, Ryan MT, Amor DJ, Fletcher JM, Dixon JW, Collins FA, Turnbull DM, Taylor RW, Thorburn DR (January 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. S2CID 21076359.
  14. 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 (April 2012). "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing" (PDF). Journal of Medical Genetics. 49 (4): 277–83. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. S2CID 3177674.
  15. 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.
  16. 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.
  17. 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 (BBA) - Bioenergetics. 1364 (2): 271–86. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934.
  18. Zafeiriou DI, Rodenburg RJ, Scheffer H, van den Heuvel LP, Pouwels PJ, Ververi A, Athanasiadou-Piperopoulou F, van der Knaap MS (June 2008). "MR spectroscopy and serial magnetic resonance imaging in a patient with mitochondrial cystic leukoencephalopathy due to complex I deficiency and NDUFV1 mutations and mild clinical course". Neuropediatrics. 39 (3): 172–5. doi:10.1055/s-0028-1093336. PMID 18991197.
  19. Laugel V, This-Bernd V, Cormier-Daire V, Speeg-Schatz C, de Saint-Martin A, Fischbach M (January 2007). "Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations". Pediatric Neurology. 36 (1): 54–7. doi:10.1016/j.pediatrneurol.2006.08.007. PMID 17162199.
  20. "103 binary interactions found for search term NDUFV1". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-27.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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