Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals
Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals
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DOI：
10.1073/pnas.0405432101
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发表时间：
2004-11-23
影响因子：
11.1
通讯作者：
Clementi, E
中科院分区：
文献类型：
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作者：
Nisoli, E;Falcone, S;Clementi, E
我们最近发现，长期暴露于一氧化氮（NO）触发线粒体生物合成在哺乳动物细胞和组织的鸟苷酸环化酶的激活和cGMP的产生。在这里，我们报告说，NO/cGMP依赖的线粒体生物合成与增强耦合呼吸和ATIP在U937，L 6和PC 12细胞的内容。观察到的ATIP含量的增加完全依赖于氧化磷酸化，因为糖酵解形成的ATP是不变的。来自内皮NO合酶无效突变小鼠的脑、肾、肝、心脏和腓肠肌显示与显著较低的耗氧量和ATIP含量相关的线粒体含量显著降低。在这些组织中，超微结构分析显示线粒体明显较小。此外，在腓肠肌肌膜下区域观察到线粒体数量显著减少。我们得出结论，NO/cGMP刺激线粒体生物合成，在体外和体内，这种刺激与增加线粒体功能，导致增强ATIP的形成。
We recently found that long-term exposure to nitric oxide (NO) triggers mitochondrial biogenesis in mammalian cells and tissues by activation of guanylate cyclase and generation of cGMP. Here, we report that the NO/cGMP-dependent mitochondrial biogenesis is associated with enhanced coupled respiration and content of ATIP in U937, L6, and PC12 cells. The observed increase in ATIP content depended entirely on oxidative phosphorylation, because ATP formation by glycolysis was unchanged. Brain, kidney, liver, heart, and gastrocnemius muscle from endothelial NO synthase null mutant mice displayed markedly reduced mitochondrial content associated with significantly lower oxygen consumption and ATIP content. In these tissues, ultrastructural analyses revealed significantly smaller mitochondria. Furthermore, a significant reduction in the number of mitochondria was observed in the subsarcolemnal region of the gastrocnemius muscle. We conclude that NO/cGMP stimulates mitochondrial biogenesis, both in vitro and in vivo, and that this stimulation is associated with increased mitochondrial function, resulting in enhanced formation of ATIP.