COQ7: Difference between revisions
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It has been shown that mutations in the gene are associated with increased [[life expectancy|life span]].<ref name="Ewbank_1997">{{cite journal | author = Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S | title = Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1 | journal = Science | volume = 275 | issue = 5302 | pages = 980–3 |date=February 1997 | pmid = 9020081 | doi = 10.1126/science.275.5302.980 | url = | issn = }}</ref><ref name="Liu_2005"/> Defects of the gene slow down a variety of developmental and physiological processes, including the cell cycle, embryogenesis, post-embryonic growth, rhythmic behaviors and aging.<ref name="Felkai_1999">{{cite journal | author = Felkai S, Ewbank JJ, Lemieux J, Labbé JC, Brown GG, Hekimi S | title = CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans | journal = EMBO J. | volume = 18 | issue = 7 | pages = 1783–92 |date=April 1999 | pmid = 10202142 | pmc = 1171264 | doi = 10.1093/emboj/18.7.1783 | url = | issn = }}</ref> |
It has been shown that mutations in the gene are associated with increased [[life expectancy|life span]].<ref name="Ewbank_1997">{{cite journal | author = Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S | title = Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1 | journal = Science | volume = 275 | issue = 5302 | pages = 980–3 |date=February 1997 | pmid = 9020081 | doi = 10.1126/science.275.5302.980 | url = | issn = }}</ref><ref name="Liu_2005"/> Defects of the gene slow down a variety of developmental and physiological processes, including the cell cycle, embryogenesis, post-embryonic growth, rhythmic behaviors and aging.<ref name="Felkai_1999">{{cite journal | author = Felkai S, Ewbank JJ, Lemieux J, Labbé JC, Brown GG, Hekimi S | title = CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans | journal = EMBO J. | volume = 18 | issue = 7 | pages = 1783–92 |date=April 1999 | pmid = 10202142 | pmc = 1171264 | doi = 10.1093/emboj/18.7.1783 | url = | issn = }}</ref> |
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==Nuclear function== |
==Nuclear function== |
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Revision as of 13:10, 28 May 2015
The clk-1 (clock-1) gene encodes an enzyme (demethoxyubiquinone monooxygenase) that is necessary for ubiquinone biosynthesis in the worm Caenorhabditis elegans and other eukaryotes. The mouse version of the gene is called mclk-1 and the human, fruit fly and yeast homolog COQ7 (coenzyme Q biosynthesis protein 7).[1][2]
CLK-1 is not to be confused with the unrelated human protein CLK1 which plays a role in RNA splicing.
Structure
The protein has two repeats of approximately 90 amino acids, that contain two conserved motifs predicted to be important for coordination of iron. The structure and function of the gene are highly conserved among different species.[3]
The C. elegans protein contains 187 amino acid residues (20 kilodaltons), the human homolog 217 amino acid residues (24 kilodaltons, gene consisting of six exons spanning 11 kb and located on chromosome 16).[4]
Mitochondrial function
Ubiquinone is a small redox active lipid that is found in most cellular membranes where it acts as a cofactor in numerous cellular redox processes, including mitochondrial electron transport. As a cofactor, ubiquinone is often involved in processes that produce reactive oxygen species (ROS). In addition, ubiquinone is one of the main endogenous antioxidants of the cell. The CLK-1 enzyme is responsible for the hydroxylation of 5-demethoxyubiquinone to 5-hydroxyubiquinone.
It has been shown that mutations in the gene are associated with increased life span.[1][3] Defects of the gene slow down a variety of developmental and physiological processes, including the cell cycle, embryogenesis, post-embryonic growth, rhythmic behaviors and aging.[5]
Nuclear function
CLK-1 and COQ7 predominantly localise to mitochondria to participate in the ubiquinone biosynthetic pathway which is localised there. However, a small pool of CLK-1 and COQ7 translocates to the nucleus in response to the production of ROS by normally functioning mitochondria in both worms and human cells, respectively[6]. Translocation of CLK-1 and COQ7 represents a mitochondrial to nuclear retrograde signalling pathway that acts to suppress mitochondrial stress responses. The mitochondrial and nuclear pools of CLK-1 are thought to contribute independently to worm lifespan regulation. The nuclear form of CLK-1 and COQ7 is thought to regulate gene expression through an unidentified mechanism.
References
- ^ a b Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S (February 1997). "Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1". Science. 275 (5302): 980–3. doi:10.1126/science.275.5302.980. PMID 9020081.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: COQ7 coenzyme Q7 homolog, ubiquinone (yeast)".
- ^ a b Liu X, Jiang N, Hughes B, Bigras E, Shoubridge E, Hekimi S (October 2005). "Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice". Genes Dev. 19 (20): 2424–34. doi:10.1101/gad.1352905. PMC 1257397. PMID 16195414.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Asaumi S, Kuroyanagi H, Seki N, Shirasawa T (June 1999). "Orthologues of the Caenorhabditis elegans longevity gene clk-1 in mouse and human". Genomics. 58 (3): 293–301. doi:10.1006/geno.1999.5838. PMID 10373327.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Felkai S, Ewbank JJ, Lemieux J, Labbé JC, Brown GG, Hekimi S (April 1999). "CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans". EMBO J. 18 (7): 1783–92. doi:10.1093/emboj/18.7.1783. PMC 1171264. PMID 10202142.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Monaghan RM, Barnes RG, Fisher K, Andreou T, Rooney N, Poulin GB, Whitmarsh AJ (June 2015). "A nuclear role for the respiratory enzyme CLK-1 in regulating mitochondrial stress responses and longevity". Nature Cell Biology. doi:10.1038/ncb3170. PMID 25961505.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
Further reading
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K; et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Jonassen T, Proft M, Randez-Gil F; et al. (1998). "Yeast Clk-1 homologue (Coq7/Cat5) is a mitochondrial protein in coenzyme Q synthesis". J. Biol. Chem. 273 (6): 3351–7. doi:10.1074/jbc.273.6.3351. PMID 9452453.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Asaumi S, Kuroyanagi H, Seki N, Shirasawa T (1999). "Orthologues of the Caenorhabditis elegans longevity gene clk-1 in mouse and human". Genomics. 58 (3): 293–301. doi:10.1006/geno.1999.5838. PMID 10373327.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Vajo Z, King LM, Jonassen T; et al. (2000). "Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging". Mamm. Genome. 10 (10): 1000–4. doi:10.1007/s003359901147. PMID 10501970.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Wiemann S, Weil B, Wellenreuther R; et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Simpson JC, Wellenreuther R, Poustka A; et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Stenmark P, Grünler J, Mattsson J; et al. (2001). "A new member of the family of di-iron carboxylate proteins. Coq7 (clk-1), a membrane-bound hydroxylase involved in ubiquinone biosynthesis". J. Biol. Chem. 276 (36): 33297–300. doi:10.1074/jbc.C100346200. PMID 11435415.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Takahashi M, Asaumi S, Honda S; et al. (2001). "Mouse coq7/clk-1 orthologue rescued slowed rhythmic behavior and extended life span of clk-1 longevity mutant in Caenorhabditis elegans". Biochem. Biophys. Res. Commun. 286 (3): 534–40. doi:10.1006/bbrc.2001.5439. PMID 11511092.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Rea S (2002). "CLK-1/Coq7p is a DMQ mono-oxygenase and a new member of the di-iron carboxylate protein family". FEBS Lett. 509 (3): 389–94. doi:10.1016/S0014-5793(01)03099-X. PMID 11749961.
- Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Wiemann S, Arlt D, Huber W; et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Mehrle A, Rosenfelder H, Schupp I; et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
- COQ7 human gene location in the UCSC Genome Browser.
- COQ7 human gene details in the UCSC Genome Browser.
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