Gertz Melanie, Steegborn Clemens
Department of Physiological Chemistry, Ruhr-University Bochum, Bochum, Germany.
Biochim Biophys Acta. 2010 Aug;1804(8):1658-65. doi: 10.1016/j.bbapap.2009.09.011. Epub 2009 Sep 18.
Sirtuins are a family of protein deacetylases that catalyze the nicotinamide adenine dinucleotide (NAD(+))-dependent removal of acetyl groups from modified lysine side chains in various proteins. Sirtuins act as metabolic sensors and influence metabolic adaptation but also many other processes such as stress response mechanisms, gene expression, and organismal aging. Mammals have seven Sirtuin isoforms, three of them - Sirt3, Sirt4, and Sirt5 - located to mitochondria, our centers of energy metabolism and apoptosis initiation. In this review, we shortly introduce the mammalian Sirtuin family, with a focus on the mitochondrial isoforms. We then discuss in detail the current knowledge on the mitochondrial isoform Sirt5. Its physiological role in metabolic regulation has recently been confirmed, whereas an additional function in apoptosis regulation remains speculative. We will discuss the biochemical properties of Sirt5 and how they might contribute to its physiological function. Furthermore, we discuss the potential use of Sirt5 as a drug target, structural features of Sirt5 and of an Sirt5/inhibitor complex as well as their differences to other Sirtuins and the current status of modulating Sirt5 activity with pharmacological compounds.
沉默调节蛋白是一类蛋白质脱乙酰酶家族，可催化烟酰胺腺嘌呤二核苷酸（NAD(+)）依赖的从各种蛋白质中修饰的赖氨酸侧链上去除乙酰基的过程。沉默调节蛋白作为代谢传感器，不仅影响代谢适应，还影响许多其他过程，如应激反应机制、基因表达和机体衰老。哺乳动物有七种沉默调节蛋白亚型，其中三种——Sirt3、Sirt4和Sirt5——定位于线粒体，即我们的能量代谢和细胞凋亡启动中心。在本综述中，我们简要介绍哺乳动物沉默调节蛋白家族，重点关注线粒体亚型。然后，我们详细讨论关于线粒体亚型Sirt5的现有知识。其在代谢调节中的生理作用最近已得到证实，而在细胞凋亡调节中的额外功能仍具有推测性。我们将讨论Sirt5的生化特性以及它们如何可能有助于其生理功能。此外，我们讨论了Sirt5作为药物靶点的潜在用途、Sirt5和Sirt5/抑制剂复合物的结构特征，以及它们与其他沉默调节蛋白的差异，以及用药理化合物调节Sirt5活性的现状。
