Impact of nitric oxide on metabolism in health and age-related disease.
Impact of nitric oxide on metabolism in health and age-related disease.
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DOI：
10.1111/j.1463-1326.2010.01267.x
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Bossy-Wetzel E
中科院分区：
文献类型：
--
作者：
Knott AB;Bossy-Wetzel E
一氧化氮（NO）在多种生理系统中充当信使分子，并且还转化为毒性自由基物质，其可通过称为亚硝化应激的过程损害细胞。虽然NO在血管扩张、神经系统和免疫系统中的生理作用已经得到很好的确立，但最近的研究已经开始研究NO通过调节线粒体在代谢和能量消耗中的作用。在某些情况下，NO似乎通过激活蛋白质如过氧化物酶体增殖物激活受体γ（PPARγ）共激活因子1α（PGC 1-α）来刺激线粒体生物合成。由于NO和线粒体生物合成之间的这种联系，NO在代谢的某些方面，包括运动反应、肥胖、脂肪细胞分化和热量限制中的作用是越来越多的研究的主题。除了其在线粒体生物发生中的作用外，NO还刺激线粒体片段化，这可能是由过多的线粒体分裂或线粒体融合的抑制引起的，并且可能导致生物能量衰竭。虽然NO介导的线粒体片段化对神经退行性疾病的贡献似乎是明确的，但NO导致片段化的机制是不确定的和有争议的。在这篇综述中，我们讨论了NO在线粒体生物发生和动力学的操纵中的作用，以及这些事件如何有助于人类健康和年龄相关疾病。
Nitric oxide (NO) serves as a messenger molecule in a variety of physiological systems and also converts into toxic radical species that can damage cells through a process known as nitrosative stress. While the physiological role of NO in blood vessel dilation, the nervous system, and the immune system is well established, recent studies have begun to investigate the role of NO in metabolism and energy expenditure through modulation of mitochondria. NO appears to stimulate mitochondrial biogenesis in certain situations through activation of proteins such as peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC1-α). Because of this link between NO and mitochondrial biogenesis, the role of NO in certain aspects of metabolism, including exercise response, obesity, fat cell differentiation, and caloric restriction, are the subject of increasing investigation. In addition to its role in mitochondrial biogenesis, NO also stimulates mitochondrial fragmentation, which can be caused by too much mitochondrial fission or inhibition of mitochondrial fusion and can result in bioenergetic failure. While the contribution of NO-mediated mitochondrial fragmentation to neurodegenerative diseases seems clear, the mechanisms by which NO causes fragmentation are uncertain and controversial. In this review, we discuss the role of NO in manipulation of mitochondrial biogenesis and dynamics and how these events contribute to human health and age-related disease.
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