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* {{UCSC genome browser|COQ7}}
* {{UCSC genome browser|COQ7}}
* {{UCSC gene details|COQ7}}
* {{UCSC gene details|COQ7}}

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[[Category:Caenorhabditis elegans genes]]
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[[Category:Ageing]]
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[[Category:Aging-related genes]]


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Revision as of 04:42, 31 December 2015

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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 lifespan.[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 found 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

  1. ^ 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)
  2. ^ "Entrez Gene: COQ7 coenzyme Q7 homolog, ubiquinone (yeast)".
  3. ^ 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)
  4. ^ 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)
  5. ^ 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)
  6. ^ 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. 17: 782–92. doi:10.1038/ncb3170. PMID 25961505.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading