Mitochondrial 5-demethoxyubiquinone hydroxylase (DMQ hydroxylase), also known as coenzyme Q7, hydroxylase, is an
enzyme that in humans is encoded by the COQ7gene. The clk-1 (clock-1) gene encodes this
protein 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).[5][6]
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.[7]
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).[8]
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
mitochondrialelectron 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.[5][7] 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.[9]
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.[10] 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.
^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.
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10.1006/geno.1999.5838.
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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.
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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:
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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.
PMID10373327.
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.
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