COQ7

The clk-1 (clock-1) is_associated_with::gene encodes an is_associated_with::enzyme (demethoxyubiquinone monooxygenase) that is necessary for is_associated_with::ubiquinone biosynthesis in the worm is_associated_with::Caenorhabditis elegans and other is_associated_with::eukaryotes. The is_associated_with::mouse version of the gene is called mclk-1 and the human, fruit fly and yeast homolog COQ7 (coenzyme Q biosynthesis protein 7).

CLK-1 is not to be confused with the unrelated human protein is_associated_with::CLK1 which plays a role in is_associated_with::RNA splicing.

Structure
The protein has two repeats of approximately 90 is_associated_with::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.

The C. elegans protein contains 187 amino acid residues (20 is_associated_with::kilodaltons), the human homolog 217 amino acid residues (24 kilodaltons, gene consisting of six is_associated_with::exons spanning 11 kb and located on is_associated_with::chromosome 16).

Mitochondrial function
is_associated_with::Ubiquinone is a small redox active is_associated_with::lipid that is found in most cellular membranes where it acts as a cofactor in numerous cellular redox processes, including is_associated_with::mitochondrial is_associated_with::electron transport. As a cofactor, ubiquinone is often involved in processes that produce is_associated_with::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. 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.

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. 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.