Mitochondrial oxidative phosphorylation is defective in the long-lived mutant clk-1
Mitochondrial oxidative phosphorylation is defective in the long-lived mutant clk-1
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DOI：
10.1074/jbc.m403066200
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发表时间：
2004-12-24
影响因子：
4.8
通讯作者：
Hoppel, CL
中科院分区：
文献类型：
--
作者：
Kayser, EB;Sedensky, MM;Hoppel, CL
秀丽隐杆线虫长寿突变体CLK-1不能合成辅酶Q(9)。相反，突变体积累了去甲氧基辅酶Q(9)和少量的罗丹酚(9)以及饮食辅酶Q(8)。我们发现，在NADH连接的电子供体(即复杂的I依赖底物)驱动的CLK-1线粒体中，氧化磷酸化存在严重缺陷，氧化磷酸化是对线粒体整体功能的测试。从络合物I到需要苯二酚的络合物III的电子转移被严重抑制，而单独的络合物则完全活跃。相比之下，通过络合物II启动的氧化磷酸化是完全正常的，这也需要苯二酚。在这里，我们显示了配合物I和II在使用CLK-1中的苯酚库的能力上的不同。这是首次直接证明了络合物I和络合物II与内源性苯苷库的差异性相互作用。这项研究结合了分子遗传学和生物化学的力量，强调了苯二酚在线粒体功能和衰老中的作用。
The long-lived mutant of Caenorhabditis elegans, clk-1, is unable to synthesize ubiquinone, CoQ(9). Instead, the mutant accumulates demethoxyubiquinone(9) and small amounts of rhodoquinone(9) as well as dietary CoQ(8). We found a profound defect in oxidative phosphorylation, a test of integrated mitochondrial function, in clk-1 mitochondria fueled by NADH-linked electron donors, i.e. complex I-dependent substrates. Electron transfer from complex I to complex III, which requires quinones, is severely depressed, whereas the individual complexes are fully active. In contrast, oxidative phosphorylation initiated through complex II, which also requires quinones, is completely normal. Here we show that complexes I and II differ in their ability to use the quinone pool in clk-1. This is the first direct demonstration of a differential interaction of complex I and complex II with the endogenous quinone pool. This study uses the combined power of molecular genetics and biochemistry to highlight the role of quinones in mitochondrial function and aging.