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小鼠coq7/clk-1同源物挽救了秀丽隐杆线虫clk-1长寿突变体的节律行为减缓并延长了其寿命。

Mouse coq7/clk-1 orthologue rescued slowed rhythmic behavior and extended life span of clk-1 longevity mutant in Caenorhabditis elegans.

作者信息

Takahashi M, Asaumi S, Honda S, Suzuki Y, Nakai D, Kuroyanagi H, Shimizu T, Honda Y, Shirasawa T

机构信息

Department of Molecular Genetics, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.

出版信息

Biochem Biophys Res Commun. 2001 Aug 24;286(3):534-40. doi: 10.1006/bbrc.2001.5439.

Abstract

The coq7/clk-1 gene was isolated from the long-lived mutant of Caenorhabditis elegans and was suggested to play a regulatory role in biological rhythm and longevity. The mouse COQ7 is homologous to Saccharomyces cerevisiae COQ7/CAT5 that is required for the biosynthesis of coenzyme Q (ubiquinone), an essential messenger in mitochondrial respiration. In the present study, we characterized the expression and processing of mouse COQ7. We found that COQ7 is highly expressed in tissues with high energy demand such as heart, muscle, liver, and kidney in mice. Biochemical analysis revealed that COQ7 is targeted to mitochondria where it is processed to mature form. Transgenic expression of mouse coq7 completely rescued the slowed rhythmic behaviors of clk-1 such as defecation. In life-span analysis, transgenic expression reverted the extended life span of clk-1 to the comparable level with wild-type control. These data strongly suggested that coq7 plays a pivotal role in the regulation of biological rhythms and the determination of life span in mammalian species.

摘要

coq7/clk-1基因是从秀丽隐杆线虫的长寿突变体中分离出来的,据推测它在生物节律和寿命方面发挥着调节作用。小鼠COQ7与酿酒酵母COQ7/CAT5同源,后者是辅酶Q(泛醌)生物合成所必需的,而辅酶Q是线粒体呼吸中的一种重要信使。在本研究中,我们对小鼠COQ7的表达和加工过程进行了表征。我们发现COQ7在小鼠体内能量需求高的组织如心脏、肌肉、肝脏和肾脏中高度表达。生化分析表明,COQ7定位于线粒体,在那里它被加工成成熟形式。小鼠coq7的转基因表达完全挽救了clk-1的节律行为减慢,如排便。在寿命分析中,转基因表达使clk-1延长的寿命恢复到与野生型对照相当的水平。这些数据有力地表明,coq7在哺乳动物物种的生物节律调节和寿命决定中起着关键作用。

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