Clementi Emilio, Nisoli Enzo
E. Medea Scientific Institute, 23842 Bosisio Parini, Italy.
Comp Biochem Physiol A Mol Integr Physiol. 2005 Oct;142(2):102-10. doi: 10.1016/j.cbpb.2005.04.022. Epub 2005 Aug 8.
Mitochondria, the site of oxidative energy metabolism in eukariotic cells, are a highly organised structure endowed with different enzymes and reactions localized in discrete membranes and aqueous compartments. Mitochondrial function is regulated in complex ways by several agonists and environmental conditions, through activation of specific transcription factors and signalling pathways. A key player in this scenario is nitric oxide (NO). Its binding to cytochrome c oxidase in the mitochondrial respiratory chain, which is reversible and in competition with oxygen, plays a role in acute oxygen sensing and in the cell response to hypoxia. Evidence of the last two years showed that NO has also long-term effects, leading to biogenesis of functionally active mitochondria, that complement its oxygen sensing function. Mitochondrial biogenesis is triggered by NO through activation of guanylate cyclase and generation of cyclic GMP, and yields formation of functionally active mitochondria. Thus, the combined action of NO at its two known intracellular receptors, cytochrome c oxidase and guanylate cyclase, appears to play a role in coupling energy generation with energy demand. This may explain why dysregulation of the NO signalling pathway is often associated with the pathogenesis of metabolic disorders.
线粒体是真核细胞中氧化能量代谢的场所，是一种高度有组织的结构，具有位于离散膜和水相区室中的不同酶和反应。线粒体功能受到多种激动剂和环境条件的复杂调节，通过特定转录因子和信号通路的激活来实现。在这种情况下，一个关键因素是一氧化氮（NO）。它与线粒体呼吸链中的细胞色素c氧化酶结合，这种结合是可逆的且与氧气竞争，在急性氧感知和细胞对缺氧的反应中发挥作用。过去两年的证据表明，NO也具有长期效应，可导致功能活跃的线粒体生物发生，这补充了其氧感知功能。NO通过激活鸟苷酸环化酶和生成环鸟苷酸触发线粒体生物发生，并产生功能活跃的线粒体。因此，NO在其两个已知的细胞内受体——细胞色素c氧化酶和鸟苷酸环化酶上的联合作用，似乎在将能量产生与能量需求相耦合中发挥作用。这可能解释了为什么NO信号通路的失调常常与代谢紊乱的发病机制相关。
