Drosophila sbo regulates lifespan through its function in the synthesis of coenzyme Q in vivo
Drosophila sbo regulates lifespan through its function in the synthesis of coenzyme Q in vivo
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果蝇 sbo 通过体内合成辅酶 Q 的功能调节寿命
DOI：
10.1016/j.jgg.2011.05.002
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发表时间：
2011-06-01
影响因子：
5.9
通讯作者：
Jiao, Renjie
中科院分区：
文献类型：
--
作者：
Liu, Jiyong;Wu, Qinghua;Jiao, Renjie
辅酶Q是真核生物和原核生物线粒体呼吸链中的重要电子载体。它由苯醌头基和疏水性聚类异戊二烯尾基组成。参与辅酶Q生物合成的基因（COQ 1 -9）已经在酵母中表征。在这项研究中，我们产生和分子特征的突变等位基因的一种新的果蝇基因，sbo，它编码的蛋白质，预计催化异戊烯化的对羟基苯甲酸酯与类异戊二烯链的辅酶Q合成的过程中。sbo在酵母中的表达挽救了Delta COQ 2突变细胞的致死性，表明sbo是COQ 2的功能同源物。HPLC结果显示，sbo杂合子果蝇体内CoQ（9）和CoQ（10）水平显著降低。此外，sbo杂合子的男性和女性的平均寿命分别延长了12.5%和30.8%。纯合子sbo动物表现出胰岛素/胰岛素样生长因子信号传导（IIS）途径的活性降低。综上所述，我们得出结论，sbo是果蝇发育所必需的基因，其突变导致寿命延长最有可能通过改变内源性辅酶Q的生物合成。
CoQ is an essential electron carrier in the mitochondrial respiratory chain of both eukaryotes and prokaryotes. It consists of a benzoquinone head group and a hydrophobic polyisoprenoid tail. The genes (COQ1-9) involved in CoQ biosynthesis have been characterized in yeast. In this study, we generated and molecularly characterized a mutant allele of a novel Drosophila gene, sbo, which encodes a protein that is predicted to catalyze the prenylation of p-hydroxybenzoate with the isoprenoid chain during the process of CoQ synthesis. Expression of sbo in yeast rescues the lethality of Delta COQ2 mutant cells, indicating that sbo is a functional homolog of COQ2. HPLC results show that the levels of CoQ(9) and CoQ(10) were significantly reduced in sbo heterozygous adult flies. Furthermore, the mean lifespans of males and females heterozygous for sbo are extended by 12.5% and 30.8%, respectively. Homozygous sbo animals exhibit reduced activities of the insulin/insulin-like growth factor signaling (IIS) pathway. Taken together, we conclude that sbo is an essential gene for Drosophila development, mutation of which leads to an extension of lifespan most likely by altering endogenous CoQ biosynthesis.