Acuña-Castroviejo Darío, Escames Germaine, López Luis C, Hitos Ana B, León Josefa
Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Granada, Spain.
Endocrine. 2005 Jul;27(2):159-68. doi: 10.1385/ENDO:27:2:159.
The presence of nitric oxide (NO* ) in the mitochondria led to analysis of its source and functions in mitochondrial homeostasis. Studies have revealed the existence of a mtNOS isoform with similar features to nNOS, with some post-traslational modifications, although without the typical signal peptide responsible for addressing proteins to mitochondrion. This isoform may account for the physiological production of NO* related to the respiratory control. During inflammatory conditions there is an excess of NO* in the mitochondria responsible for an increase in reactive oxygen and nitrogen species in sufficient amounts to compromise mitochondrial function. These conditions led to the discovery of the presence of an inducible mtNOS isoform with kinetic properties similar to iNOS. Experiments with knockout mice lacking either nNOS or iNOS further confirmed the existence of these two mtNOS isoforms in mitochondria. Although the increase in NO* in sepsis by inducible mtNOS may have important regulatory functions including the redistribution of oxygen into other pathways under hypoxia, it causes the production of excess NO* that is deleterious for the cell. Melatonin, an endogenous antioxidant, regulates mitochondrial respiration and bioenergetics and protects mitochondria from excess NO* by controlling the activity of mtNOS.
线粒体中一氧化氮（NO*）的存在促使人们对其来源及其在线粒体稳态中的功能进行分析。研究表明，存在一种与神经元型一氧化氮合酶（nNOS）具有相似特征的线粒体一氧化氮合酶（mtNOS）亚型，尽管没有负责将蛋白质转运至线粒体的典型信号肽，但存在一些翻译后修饰。这种亚型可能解释了与呼吸控制相关的NO的生理性产生。在炎症状态下，线粒体中存在过量的NO，导致活性氧和活性氮大量增加，足以损害线粒体功能。这些情况促使人们发现存在一种诱导型mtNOS亚型，其动力学特性与诱导型一氧化氮合酶（iNOS）相似。对缺乏nNOS或iNOS的基因敲除小鼠进行的实验进一步证实了线粒体中这两种mtNOS亚型的存在。尽管诱导型mtNOS在脓毒症中导致的NO增加可能具有重要的调节功能，包括在缺氧状态下将氧气重新分配至其他途径，但它会导致产生对细胞有害的过量NO。褪黑素是一种内源性抗氧化剂，可调节线粒体呼吸和生物能量学，并通过控制mtNOS的活性保护线粒体免受过量NO*的影响。
