PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure.
PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure.
复制标题
DOI：
10.1097/mol.0b013e328328d0a4
复制
发表时间：
2009-04
影响因子：
4.4
通讯作者：
Auwerx J
中科院分区：
文献类型：
--
作者：
Cantó C;Auwerx J
PGC-1α被广泛描述为线粒体生物合成的主要调节因子。然而，PGC-1α活性不是恒定的，可以根据不同的代谢情况进行微调。从这个角度来看，PGC-1α可以被描述为代谢传感器触发的转录输出的介导者，提供了这些传感器与PGC-1α一起编织控制细胞能量消耗的网络的想法。在这篇综述中，我们将重点关注2型糖尿病和代谢综合征等病理可能与该网络的异常和不适当功能有关。AMPK和SIRT 1这两种代谢传感器分别通过磷酸化和脱乙酰化直接影响PGC-1α的活性。虽然这些修饰的生理相关性及其分子后果在很大程度上仍然是未知的，但最近对不同体内转基因模型的研究清楚地表明，AMPK，SIRT 1和PGC-1α可能作为一个协调的网络来改善代谢适应性。AMPK和SIRT 1等代谢传感器是线粒体主要调节因子PGC 1 α活性的守门人，是代谢稳态调节网络中的重要环节。这些参与者共同解释了身体活动和饮食干预在我们与2型糖尿病和相关代谢紊乱的斗争中的许多有益作用。因此，了解它们的作用机制可以指导我们识别和改善代谢性疾病的预防和治疗策略。
PGC-1α has been extensively described as a master regulator of mitochondrial biogenesis. However, PGC-1α activity is not constant, and can be finely tuned in response to different metabolic situations. From this point of view, PGC-1α could be described as a mediator of the transcriptional outputs triggered by metabolic sensors, providing the idea that these sensors, together with PGC-1α, might be weaving a network controlling cellular energy expenditure. In this review we will focus on how pathologies such as type 2 diabetes and the metabolic syndrome might be related to an abnormal and improper function of this network. Two metabolic sensors, AMPK and SIRT1 have been described to directly affect PGC-1α activity through phosphorylation and deacetylation, respectively. While the physiological relevance of these modifications and their molecular consequences are still largely unknown, recent insight from different in vivo transgenic models clearly suggests that AMPK, SIRT1 and PGC-1α might act as an orchestrated network to improve metabolic fitness. Metabolic sensors such as AMPK and SIRT1, gatekeepers of the activity of the master regulator of mitochondria, PGC1α, are vital links in a regulatory network for metabolic homeostasis. Together these players explain many of the beneficial effects of physical activity and dietary interventions in our battle against type 2 diabetes and related metabolic disorders. Hence, understanding the mechanisms by which they act could guide us to identify and improve preventive and therapeutic strategies for metabolic diseases.