Laboratory of Cardiac Energetics, National Heart Lung and Blood Institute, Department of Health and Human Services, Bethesda, Maryland, USA.
Environ Mol Mutagen. 2010 Jun;51(5):352-9. doi: 10.1002/em.20574.
The nuclear DNA transcriptional programming of the mitochondria proteome varies dramatically between tissues depending on its functional requirements. This programming generally regulates all of the proteins associated with a metabolic or biosynthetic pathway associated with a given function, essentially regulating the maximum rate of the pathway while keeping the enzymes at the same molar ratio. This may permit the same regulatory mechanisms to function at low- and high-flux capacity situations. This alteration in total protein content results in rather dramatic changes in the mitochondria proteome between tissues. A tissues mitochondria proteome also changes with disease state, in Type 1 diabetes the liver mitochondrial proteome shifts to support ATP production, urea synthesis, and fatty acid oxidation. Acute flux regulation is modulated by numerous posttranslational events that also are highly variable between tissues. The most studied posttranslational modification is protein phosphorylation, which is found all of the complexes of oxidative phosphorylation and most of the major metabolic pathways. The functional significance of these modifications is currently a major area of research along with the kinase and phosphatase regulatory network. This near ubiquitous presence of protein phosphorylations, and other posttranslational events, in the matrix suggest that not all posttranslational events have functional significance. Screening methods are being introduced to detect the active or dynamic posttranslational sites to focus attention on sites that might provide insight into regulatory mechanisms.
线粒体蛋白质组的核 DNA 转录编程因组织的功能需求而在不同组织之间发生巨大变化。这种编程通常调节与特定功能相关的代谢或生物合成途径相关的所有蛋白质，本质上调节途径的最大速率，同时使酶保持相同的摩尔比。这可能允许相同的调节机制在低通量和高通量情况下发挥作用。这种总蛋白质含量的变化导致组织之间线粒体蛋白质组的相当大的变化。组织的线粒体蛋白质组也会随着疾病状态而改变，在 1 型糖尿病中，肝脏线粒体蛋白质组向支持 ATP 生成、尿素合成和脂肪酸氧化转移。急性通量调节受许多翻译后事件的调节，这些事件在组织之间也高度可变。研究最多的翻译后修饰是蛋白质磷酸化，它存在于氧化磷酸化的所有复合物和大多数主要代谢途径中。这些修饰的功能意义目前是一个主要的研究领域，还有激酶和磷酸酶调节网络。这些翻译后事件，包括蛋白质磷酸化，在基质中几乎普遍存在，这表明并非所有翻译后事件都具有功能意义。正在引入筛选方法来检测活性或动态翻译后位点，以关注可能为调节机制提供见解的位点。
