Nitrite Reductase Activity of Cytochrome c
Nitrite Reductase Activity of Cytochrome c
复制标题
DOI：
10.1074/jbc.m806934200
复制
发表时间：
2008-11-21
影响因子：
4.8
通讯作者：
Kim-Shapiro, Daniel B.
中科院分区：
文献类型：
--
作者：
Basu, Swati;Azarova, Natalia A.;Kim-Shapiro, Daniel B.
现在已经证明生理亚硝酸盐浓度的小幅增加可以介导许多生物反应，包括缺氧血管舒张、缺血/再灌注后的细胞保护以及基因和蛋白质表达的调节。因此，虽然亚硝酸盐直到最近才被认为是生物惰性的，但它现在被认为是一种潜在的重要的缺氧信号分子和治疗剂。亚硝酸盐通过与几种含血红素的蛋白反应还原为一氧化氮，介导信号传导。在这篇报道中，我们首次发现线粒体电子载体细胞色素c也能有效地将亚硝酸盐还原为NO。这种亚硝酸盐还原酶活性受到高度调控，因为它依赖于蛋白质中血红素铁的五配位，并在缺氧和酸性条件下发生。此外，我们证明，在亚硝酸盐存在下，五配位细胞色素c产生能够抑制线粒体呼吸的生物可利用NO。这些数据表明，细胞色素c作为一种亚硝酸盐还原酶可能在调节线粒体功能和促进细胞内缺氧、氧化还原和凋亡信号传导方面发挥重要作用。
Small increases in physiological nitrite concentrations have now been shown to mediate a number of biological responses, including hypoxic vasodilation, cytoprotection after ischemia/reperfusion, and regulation of gene and protein expression. Thus, while nitrite was until recently believed to be biologically inert, it is now recognized as a potentially important hypoxic signaling molecule and therapeutic agent. Nitrite mediates signaling through its reduction to nitric oxide, via reactions with several heme-containing proteins. In this report, we show for the first time that the mitochondrial electron carrier cytochrome c can also effectively reduce nitrite to NO. This nitrite reductase activity is highly regulated as it is dependent on pentacoordination of the heme iron in the protein and occurs under anoxic and acidic conditions. Further, we demonstrate that in the presence of nitrite, pentacoordinate cytochrome c generates bioavailable NO that is able to inhibit mitochondrial respiration. These data suggest an additional role for cytochrome c as a nitrite reductase that may play an important role in regulating mitochondrial function and contributing to hypoxic, redox, and apoptotic signaling within the cell.