Maissan Parcival, Mooij Eva J, Barberis Matteo
Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
Systems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, Surrey, UK.
Biology (Basel). 2021 Mar 4;10(3):194. doi: 10.3390/biology10030194.
Sirtuins are a family of highly conserved NAD+-dependent proteins and this dependency links Sirtuins directly to metabolism. Sirtuins' activity has been shown to extend the lifespan of several organisms and mainly through the post-translational modification of their many target proteins, with deacetylation being the most common modification. The seven mammalian Sirtuins, SIRT1 through SIRT7, have been implicated in regulating physiological responses to metabolism and stress by acting as nutrient sensors, linking environmental and nutrient signals to mammalian metabolic homeostasis. Furthermore, mammalian Sirtuins have been implicated in playing major roles in mammalian pathophysiological conditions such as inflammation, obesity and cancer. Mammalian Sirtuins are expressed heterogeneously among different organs and tissues, and the same holds true for their substrates. Thus, the function of mammalian Sirtuins together with their substrates is expected to vary among tissues. Any therapy depending on Sirtuins could therefore have different local as well as systemic effects. Here, an introduction to processes relevant for the actions of Sirtuins, such as metabolism and cell cycle, will be followed by reasoning on the system-level function of Sirtuins and their substrates in different mammalian tissues. Their involvement in the healthy metabolism and metabolic disorders will be reviewed and critically discussed.
沉默调节蛋白是一类高度保守的依赖烟酰胺腺嘌呤二核苷酸（NAD+）的蛋白质，这种依赖性将沉默调节蛋白与新陈代谢直接联系起来。已证明沉默调节蛋白的活性可延长多种生物体的寿命，主要是通过对其许多靶蛋白进行翻译后修饰，其中去乙酰化是最常见的修饰。七种哺乳动物沉默调节蛋白，即SIRT1至SIRT7，已被认为通过作为营养传感器来调节对新陈代谢和应激的生理反应，将环境和营养信号与哺乳动物的代谢稳态联系起来。此外，哺乳动物沉默调节蛋白在诸如炎症、肥胖和癌症等哺乳动物病理生理状况中发挥主要作用。哺乳动物沉默调节蛋白在不同器官和组织中的表达存在异质性，其底物也是如此。因此，哺乳动物沉默调节蛋白及其底物的功能在不同组织中可能会有所不同。因此，任何依赖沉默调节蛋白的疗法可能会产生不同的局部和全身效应。在此，先介绍与沉默调节蛋白作用相关的过程，如新陈代谢和细胞周期，然后对沉默调节蛋白及其底物在不同哺乳动物组织中的系统水平功能进行推理。将对它们在健康新陈代谢和代谢紊乱中的作用进行综述并展开批判性讨论。
