State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
J Genet Genomics. 2011 Jun 20;38(6):225-34. doi: 10.1016/j.jgg.2011.05.002. Epub 2011 May 14.
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 ∆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.
辅酶 Q 是真核生物和原核生物线粒体呼吸链中一种必需的电子载体。它由一个苯醌头部基团和一个疏水多异戊二烯尾组成。辅酶 Q 生物合成所涉及的基因(COQ1-9)已在酵母中得到鉴定。在这项研究中,我们生成并对一种新型果蝇基因 sbo 的突变等位基因进行了分子特征分析,该基因编码一种蛋白,预计在辅酶 Q 合成过程中催化对羟基苯甲酸与异戊二烯链的 prenylation。sbo 在酵母中的表达挽救了 ∆COQ2 突变细胞的致死性,表明 sbo 是 COQ2 的功能同源物。HPLC 结果表明,sbo 杂合子成年果蝇中的 CoQ(9) 和 CoQ(10)水平显著降低。此外,sbo 杂合子雄性和雌性的平均寿命分别延长了 12.5%和 30.8%。sbo 纯合子动物的胰岛素/胰岛素样生长因子信号通路(IIS)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,很可能是通过改变内源性辅酶 Q 生物合成来实现的。