Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation.-猫眼课题宝

DOI：

10.1126/scisignal.2003252

发表时间：

2013-01-01

期刊：

Science signaling

影响因子：

7.3

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Doulias PT;Tenopoulou M;Greene JL;Raju K;Ischiropoulos H

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010156/?report=classic

半胱氨酸S-亚硝基化是一种翻译后修饰，一氧化氮通过其调节蛋白质功能和信号传导。个别蛋白质的研究已经阐明了S-亚硝基化的特定功能作用，但内源性S-亚硝基化的程度，被亚硝基化的位点和S-亚硝基化的调控后果的知识仍然有限。我们使用质谱为基础的方法，以确定1011 S-亚硝基半胱氨酸残基在647蛋白质在各种小鼠组织。我们发现了参与糖酵解、代谢生成、三羧酸循环和氧化磷酸化的酶的选择性S-亚硝基化，表明这种翻译后修饰可能调节代谢和线粒体生物能量学。肝酶VLCAD（极长酰基辅酶A脱氢酶）在Cys 238处的S-亚硝基化，这在缺乏内皮型一氧化氮合酶的小鼠中是不存在的，提高了其催化效率。这些数据暗示蛋白质S-亚硝基化在线粒体中脂肪酸的β-氧化的调节中。

Cysteine S-nitrosylation is a posttranslational modification by which nitric oxide regulates protein function and signaling. Studies of individual proteins have elucidated specific functional roles for S-nitrosylation, but knowledge of the extent of endogenous S-nitrosylation, the sites that are nitrosylated, and the regulatory consequences of S-nitrosylation remains limited. We used mass spectrometry-based methodologies to identify 1011 S-nitrosocysteine residues in 647 proteins in various mouse tissues. We uncovered selective S-nitrosylation of enzymes participating in glycolysis, gluconeogenesis, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that this posttranslational modification may regulate metabolism and mitochondrial bioenergetics. S-nitrosylation of the liver enzyme VLCAD (very long acyl-CoA dehydrogenase) at Cys238, which was absent in mice lacking endothelial nitric oxide synthase, improved its catalytic efficiency. These data implicate protein S-nitrosylation in the regulation of β-oxidation of fatty acids in mitochondria.