Cancer Cell and Molecular Biology Group, Department of Biology, University of York, York, UK.
Curr Opin Oncol. 2012 Jan;24(1):68-75. doi: 10.1097/CCO.0b013e32834d813b.
SIRT1 impacts upon diverse cellular processes via its roles in the determination of chromatin structure, chromatin remodelling and gene expression. This review covers the recent discoveries linking SIRT1 with the regulation of mammalian metabolism and considers ways in which abnormal metabolism in disease may, in turn, impact upon SIRT1 because of SIRT1's functional dependency upon NAD.
Diverse signalling pathways are integrated to regulate energy metabolism and homeostasis. Such pathways involve intracellular networks and mitochondria, and also intercellular signalling within and between tissues to co-ordinate adaptive metabolic responses within the organism as a whole. Here, we outline the recent studies exploring the regulatory links between SIRT1 and mitochondrial biogenesis, cellular redox and associated metabolic pathways, and angiogenesis/Notch signalling. These links are effected by the SIRT1-mediated deacetylation of transcriptional regulators and enzymes with key roles in metabolism.
SIRT1 activity is directly coupled with homeostasis and metabolism. SIRT1 is also a metabolic sensor. It follows that disease-related metabolic abnormalities are likely to impinge upon SIRT1 functioning. Disease-related functions of SIRT1, in their turn, offer potential targets for the development of novel SIRT1-based therapies. In cancer, for example, the survival function of SIRT1 may reflect abnormal cancer metabolism and identifies SIRT1 as a target for anticancer therapy.
SIRT1 通过其在染色质结构、染色质重塑和基因表达中的作用，影响多种细胞过程。本综述涵盖了最近发现的将 SIRT1 与哺乳动物代谢调节联系起来的研究，并考虑了疾病中异常代谢可能通过 SIRT1 对 NAD 的功能依赖性反过来影响 SIRT1 的方式。
多种信号通路被整合来调节能量代谢和稳态。这些途径涉及细胞内网络和线粒体，以及细胞间信号转导，以协调整个生物体的适应性代谢反应。在这里，我们概述了最近探索 SIRT1 与线粒体生物发生、细胞氧化还原和相关代谢途径以及血管生成/Notch 信号之间调节联系的研究。这些联系是通过 SIRT1 介导的转录调节剂和在代谢中具有关键作用的酶的去乙酰化作用实现的。
SIRT1 的活性与内稳态和代谢直接相关。SIRT1 也是代谢传感器。因此，与疾病相关的代谢异常很可能影响 SIRT1 的功能。SIRT1 的疾病相关功能反过来又为基于 SIRT1 的新型治疗方法的开发提供了潜在的靶点。例如，在癌症中，SIRT1 的存活功能可能反映了异常的癌症代谢，并将 SIRT1 确定为抗癌治疗的靶点。
