A defect in coenzyme Q biosynthesis is responsible for the respiratory deficiency in Saccharomyces cerevisiae abc1 mutants
A defect in coenzyme Q biosynthesis is responsible for the respiratory deficiency in Saccharomyces cerevisiae abc1 mutants
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DOI：
10.1074/jbc.m100952200
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发表时间：
2001-05-25
影响因子：
4.8
通讯作者：
Clarke, CF
中科院分区：
文献类型：
--
作者：
Do, TQ;Hsu, AY;Clarke, CF
泛醌（辅酶Q或Q）是真核细胞线粒体呼吸链的重要组成部分。有八个互补组的Q缺陷酿酒酵母突变体，命名为coq 1-coq 8。在此，我们报道了COQ 8是ABC 1（用于be的活性，复合物），其最初作为细胞色素B mRNA翻译缺陷的多拷贝抑制剂分离（Bousquet，I.，Dujardin，G.，和Slonimski，P. P.（1991）EIMBO J. 10，2023-2031），以前对abc 1突变体的研究表明线粒体呼吸复合物是热敏性的并且功能无效。虽然abc 1突变体的初步表征显示Q缺陷突变体的特征，但据报道Q水平与野生型相似。所提出的Abc 1 p的功能是，它充当对于be及其邻近复合物的正确构象和功能所必需的伴侣样蛋白（Brasseur，G，Tron，P，Dujardin，G，Slonimski，P，P，（1997）fur. 246，103-111）。这里提出的研究表明，abc 1/coq 8无效突变体是有缺陷的Q生物合成和积累3-hexaprenyl-4-hydroxybenzoic acid作为主要中间体。如在其它酵母cog突变体中观察到的，用Q补充生长培养基拯救了abc 1/coq 8无效突变体在不可发酵碳源上生长。这种补充也部分恢复琥珀酸细胞色素c还原酶活性的abc 1/coq 8无效突变体。Abc 1/Coq 8 p定位于线粒体，并在输入时进行蛋白水解加工。这里提出的研究结果表明，以前报道的呼吸复合物的abc 1/coq 8突变体的热敏性的结果从缺乏Q和呼吸的一般缺陷，而不是一个特定的表型，由于功能障碍的Abc 1多肽。这些结果表明ABC 1/COQ 8是Q-生物合成所必需的，并且abc 1/coq 8突变体的关键缺陷是缺乏Q。
Ubiquinone (coenzyme Q or Q) is an essential component of the mitochondrial respiratory chain in eukaryotic cells. There are eight complementation groups of Q-deficient Saccharomyces cerevisiae mutants designated coq1-coq8, Here we report that COQ8 is ABC1 (for Activity of be, complex), which was originally isolated as a multicopy suppressor of a cytochrome b mRNA translation defect (Bousquet, I., Dujardin, G,, and Slonimski, P. P. (1991) EIMBO J. 10, 2023-2031), Previous studies of abc1 mutants suggested that the mitochondrial respiratory complexes were thermosensitive and function inefficiently. Although initial characterization of the abc1 mutants revealed characteristics of Q-deficient mutants, levels of Q were reported to be similar to wild type. The suggested function of Abc1p was that it acts as a chaperone-like protein essential for the proper conformation and functioning of the be, and its neighboring complexes (Brasseur, G,, Tron, P,, Dujardin, G,, Slonimski, P, P, (1997) fur. J. Biochem. 246, 103-111). Studies presented here indicate that abc1/coq8 null mutants are defective in Q biosynthesis and accumulate 3-hexaprenyl-4-hydroxybenzoic acid as the predominant intermediate. As observed in other yeast cog mutants, supplementation of growth media with Q, rescues the abc1/coq8 null mutants for growth on nonfermentable carbon sources. Such supplementation also partially restores succinate-cytochrome c reductase activity in the abc1/coq8 null mutants. Abc1/Coq8p localizes to the mitochondria, and is proteolytically processed upon import. The findings presented here indicate that the previously reported thermosensitivity of the respiratory complexes of abc1/coq8 mutants results from the lack of Q and a general deficiency in respiration, rather than a specific phenotype due to dysfunction of the Abc1 polypeptide. These results indicate that ABC1/COQ8 is essential for Q-biosynthesis and that the critical defect of abc1/coq8 mutants is a lack of Q.