Metabolic regulation by SIRT3: implications for tumorigenesis.
Metabolic regulation by SIRT3: implications for tumorigenesis.
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DOI：
10.1016/j.molmed.2012.05.004
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发表时间：
2012-09
影响因子：
13.6
通讯作者：
Haigis MC
中科院分区：
文献类型：
--
作者：
Finley LW;Haigis MC
癌细胞通过消耗高水平的营养物质和重新布线代谢以支持大分子生物合成来满足其对能量和生物质生产的需求。线粒体酶在合成代谢生长中起核心作用，乙酰化可能提供线粒体代谢途径的关键调节层。作为一种主要的线粒体脱乙酰酶，SIRT3调节酶的活性以协调细胞代谢的整体变化。SIRT3促进三羧酸（TCA）循环，电子传递链功能，并减少氧化应激。SIRT 3的缺失会引发氧化损伤、活性氧簇（ROS）介导的信号传导和代谢重编程，以支持增殖和肿瘤发生。因此，SIRT3是一个有趣的例子，说明营养敏感的翻译后调节如何提供代谢途径的综合调节，以促进响应不同营养信号的代谢稳态。
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 tricarboxylic acid (TCA) cycle, electron transport chain function, 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.