Biology:NDUFV1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial (NDUFV1) is an enzyme that in humans is encoded by the NDUFV1 gene.[1] 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.[2]

Structure

NDUFV1 is located on the q arm of chromosome 11 in position 13.2 and has 10 exons.[2] The NDUFV1 gene produces a 50.8 kDa protein composed of 464 amino acids.[3][4] 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.[2] It also contains a transit peptide domain and is composed of 6 turns, 14 beta strands, and 19 alpha helixes.[5][6]

Function

Complex I is composed of 45 different subunits. NDUFV1 is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.[7] 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.[5][6]

Catalytic Activity

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

NADH + acceptor = NAD+ + reduced acceptor.[5][6]

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.[8][9] 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.[10] However, the majority of cases are caused by mutations in nuclear-encoded genes.[11][12] 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.[13] Clinical manifestations can include lactic acidosis, cerebral degeneration, ophthalmoplegia, ataxia, spasticity, and dystonia resulting from mutations in NDUFV1.[14][15]

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.[16]

References

  1. ↑ "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. December 1992. doi:10.1016/S0888-7543(05)80144-2. PMID 1478657. 
  2. ↑ 2.0 2.1 2.2 "Entrez Gene: NDUFV1 NADH dehydrogenase (ubiquinone) flavoprotein 1, 51kDa". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4723.  This article incorporates text from this source, which is in the public domain.
  3. ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". https://amino.heartproteome.org/web/protein/P49821. 
  4. ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 
  5. ↑ 5.0 5.1 5.2 "NDUFV1 - NADH dehydrogenase [ubiquinone flavoprotein 1, mitochondrial precursor - Homo sapiens (Human) - NDUFV1 gene & protein"] (in en). https://www.uniprot.org/uniprot/P49821.  This article incorporates text available under the CC BY 4.0 license.
  6. ↑ 6.0 6.1 6.2 "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622. 
  7. ↑ "The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification". The Journal of Biological Chemistry 278 (16): 13619–22. April 2003. doi:10.1074/jbc.C300064200. PMID 12611891. 
  8. ↑ "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–45. September 2004. doi:10.1172/JCI20683. PMID 15372108. 
  9. ↑ "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. January 2004. doi:10.1002/ana.10787. PMID 14705112. 
  10. ↑ "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing". Journal of Medical Genetics 49 (4): 277–83. April 2012. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. https://epub.ub.uni-muenchen.de/21895/1/oa_21895.pdf. 
  11. ↑ "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation 15 (2): 123–34. 2000. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489. 
  12. ↑ "Respiratory chain complex I deficiency". American Journal of Medical Genetics 106 (1): 37–45. 2001. doi:10.1002/ajmg.1397. PMID 11579423. 
  13. ↑ "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. May 1998. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934. 
  14. ↑ "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. June 2008. doi:10.1055/s-0028-1093336. PMID 18991197. 
  15. ↑ "Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations". Pediatric Neurology 36 (1): 54–7. January 2007. doi:10.1016/j.pediatrneurol.2006.08.007. PMID 17162199. 
  16. ↑ "103 binary interactions found for search term NDUFV1". IntAct Molecular Interaction Database. EMBL-EBI. https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFV1. 

Further reading

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




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