Piantadosi Claude A
Departments of Medicine and Pathology, Box 3315, Duke University Medical Center, Durham, NC 27710, USA.
Biochim Biophys Acta. 2012 Jun;1820(6):712-21. doi: 10.1016/j.bbagen.2011.03.008. Epub 2011 Mar 21.
Nitric oxide (NO) exerts powerful physiological effects through guanylate cyclase (GC), a non-mitochondrial enzyme, and through the generation of protein cysteinyl-NO (SNO) adducts-a post-translational modification relevant to mitochondrial biology. A small number of SNO proteins, generated by various mechanisms, are characteristically found in mammalian mitochondria and influence the regulation of oxidative phosphorylation and other aspects of mitochondrial function.
The principles by which mitochondrial SNO proteins are formed and their actions, independently or collectively with NO binding to heme, iron-sulfur centers, or to glutathione (GSH) are reviewed on a molecular background of SNO-based signal transduction.
Mitochondrial SNO-proteins have been demonstrated to inhibit Complex I of the electron transport chain, to modulate mitochondrial reactive oxygen species (ROS) production, influence calcium-dependent opening of the mitochondrial permeability transition pore (MPTP), promote selective importation of mitochondrial protein, and stimulate mitochondrial fission. The ease of reversibility and the affirmation of regulated S-nitros(yl)ating and denitros(yl)ating enzymatic reactions support hypotheses that SNO regulates the mitochondrion through redox mechanisms. SNO modification of mitochondrial proteins, whether homeostatic or adaptive (physiological), or pathogenic, is an area of active investigation.
Mitochondrial SNO proteins are associated with mainly protective, bur some pathological effects; the former mainly in inflammatory and ischemia/reperfusion syndromes and the latter in neurodegenerative diseases. Experimentally, mitochondrial SNO delivery is also emerging as a potential new area of therapeutics. This article is part of a Special Issue entitled: Regulation of cellular processes by S-nitrosylation.
一氧化氮（NO）通过鸟苷酸环化酶（GC，一种非线粒体酶）发挥强大的生理作用，并通过生成蛋白质半胱氨酸 - NO（SNO）加合物（一种与线粒体生物学相关的翻译后修饰）发挥作用。通过各种机制产生的少量SNO蛋白，典型地存在于哺乳动物线粒体中，并影响氧化磷酸化的调节和线粒体功能的其他方面。
基于SNO的信号转导的分子背景下，综述了线粒体SNO蛋白形成的原理及其作用，这些作用包括其单独作用或与NO结合到血红素、铁硫中心或谷胱甘肽（GSH）时的共同作用。
线粒体SNO蛋白已被证明可抑制电子传递链的复合体I，调节线粒体活性氧（ROS）的产生，影响线粒体通透性转换孔（MPTP）的钙依赖性开放，促进线粒体蛋白的选择性导入，并刺激线粒体分裂。SNO修饰的可逆性以及对受调控的S-亚硝基化和去亚硝基化酶促反应的确认支持了SNO通过氧化还原机制调节线粒体的假说。线粒体蛋白的SNO修饰，无论是稳态的、适应性的（生理性的）还是致病性的，都是一个活跃的研究领域。
线粒体SNO蛋白主要与保护作用相关，但也有一些病理作用；前者主要见于炎症和缺血/再灌注综合征，后者见于神经退行性疾病。在实验中，线粒体SNO传递也正在成为一个潜在的新治疗领域。本文是名为：S-亚硝基化对细胞过程的调节的特刊的一部分。
