COQ7

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Coenzyme Q7 homolog, ubiquinone (yeast)
Identifiers
Symbols COQ7 ; CAT5; CLK-1; CLK1
External IDs OMIM601683 MGI107207 HomoloGene6953 GeneCards: COQ7 Gene
EC number 1.14.13.-
RNA expression pattern
PBB GE COQ7 209746 s at tn.png
PBB GE COQ7 209745 at tn.png
PBB GE COQ7 210820 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10229 12850
Ensembl ENSG00000167186 ENSMUSG00000030652
UniProt Q99807 P97478
RefSeq (mRNA) NM_001190983 NM_001304758
RefSeq (protein) NP_001177912 NP_001291687
Location (UCSC) Chr 16:
19.07 – 19.08 Mb
Chr 7:
118.51 – 118.53 Mb
PubMed search [1] [2]

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[edit]

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[edit]

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[edit]

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[edit]

  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. 
  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. 
  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. 
  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. 
  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. doi:10.1038/ncb3170. PMID 25961505. 

Further reading[edit]

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