Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Trends Mol Med. 2012 Sep;18(9):516-23. doi: 10.1016/j.molmed.2012.05.004. Epub 2012 Jun 27.
Cancer cells meet their needs for energy and biomass production by consuming high levels of nutrients and rewiring metabolism to support macromolecular biosynthesis. Mitochondrial enzymes play central roles in anabolic growth, and acetylation may provide a key layer of regulation over mitochondrial metabolic pathways. As a major mitochondrial deacetylase, SIRT3 regulates the activity of enzymes to coordinate global shifts in cellular metabolism. SIRT3 promotes the function of the tricarboxylic acid (TCA) cycle and the electron transport chain and reduces oxidative stress. Loss of SIRT3 triggers oxidative damage, reactive oxygen species (ROS)-mediated signaling, and metabolic reprogramming to support proliferation and tumorigenesis. Thus, SIRT3 is an intriguing example of how nutrient-sensitive, post-translational regulation may provide integrated regulation of metabolic pathways to promote metabolic homeostasis in response to diverse nutrient signals.
癌细胞通过消耗大量营养物质并重新布线代谢来支持大分子生物合成，从而满足其对能量和生物量生产的需求。线粒体酶在合成代谢生长中发挥核心作用，而乙酰化可能为调节线粒体代谢途径提供关键的调控层。作为主要的线粒体去乙酰化酶，SIRT3 通过调节酶的活性来协调细胞代谢的全局变化。SIRT3 促进三羧酸 (TCA) 循环和电子传递链的功能，并减少氧化应激。SIRT3 的缺失会引发氧化损伤、活性氧 (ROS) 介导的信号转导以及代谢重编程，以支持增殖和肿瘤发生。因此，SIRT3 是一个有趣的例子，说明了营养敏感的翻译后调节如何为代谢途径提供综合调节，以响应不同的营养信号促进代谢稳态。
