Nutrient-dependent regulation of PGC-1alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5.
Nutrient-dependent regulation of PGC-1alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5.
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DOI：
10.1016/j.bbapap.2009.11.023
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Puigserver P
中科院分区：
文献类型：
--
作者：
Dominy JE Jr;Lee Y;Gerhart-Hines Z;Puigserver P
哺乳动物拥有一个复杂的调节系统，用于控制通过燃料利用途径的通量，以响应特定常量营养素的膳食可用性。例如，在禁食条件下，哺乳动物启动全身代谢反应，限制葡萄糖利用并促进脂肪酸氧化。了解这一过程发生的潜在机制将有助于开发新的代谢紊乱治疗方法，如II型糖尿病和肥胖症。最近发现的参与代谢重编程的信号转导途径的组分之一是PGC-1α。这种转录辅激活因子能够协调参与葡萄糖和脂肪酸代谢的多种基因的表达。营养物质对PGC-1α活性的调控与其乙酰化状态密切相关。在这篇综述中，我们评估了PGC-1α活性的营养调控如何与脱乙酰酶Sirt 1和乙酰转移酶GCN 5对其乙酰化状态的调控相一致。我们还提出了一个额外的实验指令，这将有助于进一步阐明这个非常强大的转录辅激活因子的大纲。
Mammals possess an intricate regulatory system for controlling flux through fuel utilization pathways in response to the dietary availability of particular macronutrients. Under fasting conditions, for instance, mammals initiate a whole body metabolic response that limits glucose utilization and favors fatty acid oxidation. Understanding the underlying mechanisms by which this process occurs will facilitate the development of new treatments for metabolic disorders such as type II diabetes and obesity. One of the recently identified components of the signal transduction pathway involved in metabolic reprogramming is PGC-1α. This transcriptional coactivator is able to coordinate the expression of a wide array of genes involved in glucose and fatty acid metabolism. The nutrient-mediated control of PGC-1α activity is tightly correlated with its acetylation state. In this review, we evaluate how the nutrient regulation of PGC-1α activity squares with the regulation of its acetylation state by the deacetylase Sirt1 and the acetyltransferase GCN5. We also propose an outline of additional experimental directives that will help to shed additional light on this very powerful transcriptional coactivator.
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DOI：
10.1073/pnas.0808207105
发表时间：
2008-11-04
影响因子：
11.1
作者：
Coste, Agnes;Louet, Jean-Francois;Auwerx, Johan
通讯作者：
Auwerx, Johan
影响因子：
9.8
作者：
Bordone L;Motta MC;Picard F;Robinson A;Jhala US;Apfeld J;McDonagh T;Lemieux M;McBurney M;Szilvasi A;Easlon EJ;Lin SJ;Guarente L
通讯作者：
Guarente L
影响因子：
3
作者：
Beher, Dirk;Wu, John;Wang, Minghan
通讯作者：
Wang, Minghan
影响因子：
4.8
作者：
Burgess, Shawn C.;Leone, Teresa C.;Finck, Brian N.
通讯作者：
Finck, Brian N.
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere