Mitochondrial 5-demethoxyubiquinone hydroxylase (DMQ hydroxylase), also known as ''coenzyme Q7, hydroxylase'', is an
enzyme that in humans is encoded by the ''COQ7''
gene. The ''clk-1'' (''clock-1'') gene encodes this
protein that is necessary for
ubiquinone biosynthesis in the worm ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
'' and other
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s. The
mouse
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
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
CLK1 which plays a role in
RNA splicing
RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' b ...
.
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.
The ''
C. elegans'' protein contains 187 amino acid residues (20
kilodaltons), the human homolog 217 amino acid residues (24 kilodaltons, gene consisting of six
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...
s spanning 11 kb and located on
chromosome 16).
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
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
l
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.
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.
References
Further reading
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External links
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EC 1.13
Ageing
Aging-related genes
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