MT-ND4L
| ND4L | |||
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Gene ontology | |||
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Ensembl | |||||||||
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| RefSeq (protein) |
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| Location (UCSC) | Chr M: 0.01 – 0.01 Mb | Chr M: 0.01 – 0.01 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
MT-ND4L is a
Structure
The MT-ND4L gene is located in human mitochondrial DNA from base pair 10,469 to 10,765.hydrophilic domain for the peripheral arm that includes all the known redox centres and the NADH binding site. MT-ND4L and the rest of the mitochondrially encoded subunits are the most hydrophobic of the subunits of Complex I and form the core of the transmembrane region.[6]
An unusual feature of the human MT-ND4L gene is the 7-nucleotide
gene overlap of its last three codons (5'-
(+1), the MT-ND4 gene starts in the +3 reading frame: CAA TGC TAA-3' coding for Gln, Cys and Stop) with the first three codons of the MT-ND4 gene (5'-ATG CTA AAA-3' coding for amino acids Met-Leu-Lys).[9] With respect to the MT-ND4L reading frame[CAA][TGC][TAA]AA versus CA[ATG][CTA][AAA].
Function
The MT-ND4L product is a subunit of the respiratory chain
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.[6]
Clinical significance
Mitochondrial dysfunction resulting from variants of MT-ND4L, MT-ND1 and MT-ND2 have been linked to BMI in adults and implicated in metabolic disorders including obesity, diabetes and hypertension.[7]
A T>C mutation at position 10,663 in the mitochondrial gene MT-ND4L is known to cause
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000212907 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000065947 – Ensembl, May 2017
- ^ "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.
- ^ a b "Entrez Gene: MT-ND4L NADH dehydrogenase subunit 4L".
- ^ ISBN 978-0-47054784-7.
- ^ PMID 25153900.
- ^ )
- ^ a b Homo sapiens mitochondrion, complete genome. "Revised Cambridge Reference Sequence (rCRS): accession NC_012920", National Center for Biotechnology Information. Retrieved on 30 January 2016.
- PMID 23965338.
- ^ "NADH-ubiquinone oxidoreductase chain 4L". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ^ "MT-ND4L - NADH-ubiquinone oxidoreductase chain 4L - Homo sapiens (Human)". UniProt.org: a hub for protein information. The UniProt Consortium.
Further reading
- Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ (Jun 2006). "Harvesting the fruit of the human mtDNA tree". Trends in Genetics. 22 (6): 339–45. PMID 16678300.
- Bodenteich A, Mitchell LG, Polymeropoulos MH, Merril CR (May 1992). "Dinucleotide repeat in the human mitochondrial D-loop". Human Molecular Genetics. 1 (2): 140. PMID 1301157.
- Lu X, Walker T, MacManus JP, Seligy VL (Jul 1992). "Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation". Cancer Research. 52 (13): 3718–25. PMID 1377597.
- Marzuki S, Noer AS, Lertrit P, Thyagarajan D, Kapsa R, Utthanaphol P, Byrne E (Dec 1991). "Normal variants of human mitochondrial DNA and translation products: the building of a reference data base". Human Genetics. 88 (2): 139–45. S2CID 28048453.
- Moraes CT, Andreetta F, Bonilla E, Shanske S, DiMauro S, Schon EA (Mar 1991). "Replication-competent human mitochondrial DNA lacking the heavy-strand promoter region". Molecular and Cellular Biology. 11 (3): 1631–7. PMID 1996112.
- Attardi G, Chomyn A, Doolittle RF, Mariottini P, Ragan CI (1987). "Seven unidentified reading frames of human mitochondrial DNA encode subunits of the respiratory chain NADH dehydrogenase". Cold Spring Harbor Symposia on Quantitative Biology. 51. 51 (1): 103–14. PMID 3472707.
- Chomyn A, Cleeter MW, Ragan CI, Riley M, Doolittle RF, Attardi G (Oct 1986). "URF6, last unidentified reading frame of human mtDNA, codes for an NADH dehydrogenase subunit". Science. 234 (4776): 614–8. PMID 3764430.
- Chomyn A, Mariottini P, Cleeter MW, Ragan CI, Matsuno-Yagi A, Hatefi Y, Doolittle RF, Attardi G (1985). "Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase". Nature. 314 (6012): 592–7. S2CID 32964006.
- Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG (Apr 1981). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–65. S2CID 4355527.
- Montoya J, Ojala D, Attardi G (Apr 1981). "Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs". Nature. 290 (5806): 465–70. S2CID 4358928.
- Horai S, Hayasaka K, Kondo R, Tsugane K, Takahata N (Jan 1995). "Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs". Proceedings of the National Academy of Sciences of the United States of America. 92 (2): 532–6. PMID 7530363.
- Brown MD, Torroni A, Reckord CL, Wallace DC (1996). "Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations". Human Mutation. 6 (4): 311–25. S2CID 7952344.
- Arnason U, Xu X, Gullberg A (Feb 1996). "Comparison between the complete mitochondrial DNA sequences of Homo and the common chimpanzee based on nonchimeric sequences". Journal of Molecular Evolution. 42 (2): 145–52. S2CID 9082248.
- Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD, Trush MA, Kinzler KW, Vogelstein B (Nov 1998). "Somatic mutations of the mitochondrial genome in human colorectal tumours". Nature Genetics. 20 (3): 291–3. S2CID 19786796.
- Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N (Oct 1999). "Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA". Nature Genetics. 23 (2): 147. S2CID 32212178.
- Ingman M, Kaessmann H, Pääbo S, Gyllensten U (Dec 2000). "Mitochondrial genome variation and the origin of modern humans". Nature. 408 (6813): 708–13. S2CID 52850476.
- Finnilä S, Lehtonen MS, Majamaa K (Jun 2001). "Phylogenetic network for European mtDNA". American Journal of Human Genetics. 68 (6): 1475–84. PMID 11349229.
- Maca-Meyer N, González AM, Larruga JM, Flores C, Cabrera VM (2003). "Major genomic mitochondrial lineages delineate early human expansions". BMC Genetics. 2: 13. PMID 11553319.
- Herrnstadt C, Elson JL, Fahy E, Preston G, Turnbull DM, Anderson C, Ghosh SS, Olefsky JM, Beal MF, Davis RE, Howell N (May 2002). "Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups". American Journal of Human Genetics. 70 (5): 1152–71. PMID 11938495.
- Silva WA, Bonatto SL, Holanda AJ, Ribeiro-Dos-Santos AK, Paixão BM, Goldman GH, Abe-Sandes K, Rodriguez-Delfin L, Barbosa M, Paçó-Larson ML, Petzl-Erler ML, Valente V, Santos SE, Zago MA (Jul 2002). "Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America". American Journal of Human Genetics. 71 (1): 187–92. PMID 12022039.