NDUFB8 explained

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial is an enzyme that in humans is encoded by the NDUFB8 gene.^{[1] [2]} NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.^[3]

Gene

The NDUFB8 gene is located on the q arm of chromosome 10 in position 24.31 and is 6,194 base pairs long.^{[4] [5]}

Structure

The NDUFB8 protein weighs 22 kDa and is composed of 186 amino acids.^{[4] [5]} NDUFB8 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] NDUFB7 and NDUFB8 have been shown to localize at the intermembrane surface of complex I.^[6] 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.

Function

The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I) that is not directly involved in catalysis. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified.^[2] 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.

Further reading

• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Dunbar DR, Shibasaki Y, Dobbie L, Andersson B, Brookes AJ . In situ hybridisation mapping of genomic clones for five human respiratory chain complex I genes . Cytogenetics and Cell Genetics . 78 . 1 . 21–4 . 1997 . 9345899 . 10.1159/000134618 .
• Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA . 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 . Dec 1998 . 9878551 . 10.1006/bbrc.1998.9786 .
• Emahazion T, Jobs M, Howell WM, Siegfried M, Wyöni PI, Prince JA, Brookes AJ . Identification of 167 polymorphisms in 88 genes from candidate neurodegeneration pathways . Gene . 238 . 2 . 315–24 . Oct 1999 . 10570959 . 10.1016/S0378-1119(99)00330-3 .
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–60 . Oct 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . Mar 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Reports . 1 . 3 . 287–92 . Sep 2000 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .
• Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC . Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects . Atherosclerosis . 191 . 1 . 63–72 . Mar 2007 . 16806233 . 10.1016/j.atherosclerosis.2006.05.032 .
• Book: Hsieh SM, Maguire DJ, Lintell NA, McCabe M, Griffiths LR . Oxygen Transport to Tissue XXVIII . Pten and Ndufb8 Aberrations in Cervical Cancer Tissue . Advances in Experimental Medicine and Biology . 599 . 31–6 . 2007 . 17727244 . 10.1007/978-0-387-71764-7_5 . 978-0-387-71763-0 .

Notes and References

1. Emahazion T, Brookes AJ . Mapping of the NDUFA2, NDUFA6, NDUFA7, NDUFB8, and NDUFS8 electron transport chain genes by intron based radiation hybrid mapping . Cytogenetics and Cell Genetics . 82 . 1–2 . 114 . Nov 1998 . 9763676 . 10.1159/000015081 . 46861680 .
2. Web site: Entrez Gene: NDUFB8 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19kDa.
3. Book: Donald . Voet . Judith G. . Voet . Charlotte W. . Pratt . vanc . Donald Voet . Judith G. Voet . Fundamentals of biochemistry: life at the molecular level . 2013 . Wiley . Hoboken, NJ . 978-0-470-54784-7 . Chapter 18 . 581–620 . 4th .
4. 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 . Integration of cardiac proteome biology and medicine by a specialized knowledgebase . Circulation Research . 113 . 9 . 1043–53 . Oct 2013 . 23965338 . 4076475 . 10.1161/CIRCRESAHA.113.301151 .
5. Web site: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8 ]. Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) .
6. Szklarczyk R, Wanschers BF, Nabuurs SB, Nouws J, Nijtmans LG, Huynen MA . NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I . FEBS Letters . 585 . 5 . 737–43 . Mar 2011 . 21310150 . 10.1016/j.febslet.2011.01.046 . 20557524 . free .