NADH dehydrogenase (ubiquinone), alpha 1

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NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa
Identifiers
Symbols NDUFA1 ; CI-MWFE; MWFE; ZNF183
External IDs OMIM300078 MGI1929511 HomoloGene3337 GeneCards: NDUFA1 Gene
EC number 1.6.99.3
RNA expression pattern
PBB GE NDUFA1 202298 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4694 54405
Ensembl ENSG00000125356 ENSMUSG00000016427
UniProt O15239 O35683
RefSeq (mRNA) NM_004541 NM_019443
RefSeq (protein) NP_004532 NP_062316
Location (UCSC) Chr X:
119.01 – 119.01 Mb
Chr X:
37.19 – 37.19 Mb
PubMed search [1] [2]

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 is a protein that in humans is encoded by the NDUFA1 gene.[1][2] The NDUFA1 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[3] Mutations in the NDUFA1 gene are associated with mitochondrial Complex I deficiency.[2]

Structure[edit]

The NDUFA1 gene is located on the long q arm of the X chromosome at position 24 and it spans 5,176 base pairs.[2] The NDUFA1 gene produces an 8.1 kDa protein composed of 70 amino acids.[4][5] NDUFA1 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[3] NDUFA1 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.[2]

Function[edit]

The human NDUFA1 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[2] However, NDUFA1 is an accessory subunit of the complex that is believed not to be involved in catalysis.[6] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[3]

Clinical significance[edit]

Mitochondrial complex I deficiency (MT-C1D) is caused by mutations affecting the NDUFA1 gene. Complex I deficiency is a disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations, from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber's hereditary optic neuropathy, and some forms of Parkinson's disease.[2][6]

References[edit]

  1. ^ Zhuchenko O, Wehnert M, Bailey J, Sun ZS, Lee CC (Mar 1997). "Isolation, mapping, and genomic structure of an X-linked gene for a subunit of human mitochondrial complex I". Genomics 37 (3): 281–8. doi:10.1006/geno.1996.0561. PMID 8938439. 
  2. ^ a b c d e f "Entrez Gene: NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5kDa". 
  3. ^ a b c Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed. ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847. 
  4. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS et al. (Oct 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. 
  5. ^ "NDUFA1 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). 
  6. ^ a b "NDUFA1 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1". UniProt: a hub for protein information. The UniProt Consortium. Retrieved 24 March 2015. 

Further reading[edit]

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