The NDUFA1 gene is located on the long q arm of the X chromosome at position 24 and it spans 5,176 base pairs.[6] The NDUFA1 gene produces an 8.1 kDa protein composed of 70 amino acids.[8][9] NDUFA1 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobictransmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[7] 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.[6]
Function
The human NDUFA1 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[6] However, NDUFA1 is an accessory subunit of the complex that is believed not to be involved in catalysis.[10] 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.[7]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Zhuchenko O, Wehnert M, Bailey J, Sun ZS, Lee CC (November 1996). "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. PMID8938439.
^ abcDonald Voet; Judith G. Voet; Charlotte W. Pratt (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN9780470547847.
^Mayr JA, Bodamer O, Haack TB, Zimmermann FA, Madignier F, Prokisch H, Rauscher C, Koch J, Sperl W (August 2011). "Heterozygous mutation in the X chromosomal NDUFA1 gene in a girl with complex I deficiency". Molecular Genetics and Metabolism. 103 (4): 358–61. doi:10.1016/j.ymgme.2011.04.010. PMID21596602.
Tretter L, Sipos I, Adam-Vizi V (March 2004). "Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson's disease". Neurochemical Research. 29 (3): 569–77. doi:10.1023/B:NERE.0000014827.94562.4b. PMID15038604. S2CID38103900.
Frattini A, Faranda S, Bagnasco L, Patrosso C, Nulli P, Zucchi I, Vezzoni P (June 1997). "Identification of a new member (ZNF183) of the Ring finger gene family in Xq24-25". Gene. 192 (2): 291–8. doi:10.1016/S0378-1119(97)00108-X. PMID9224902.
Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA (December 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. PMID9878551.
