Compartmentalized AMPK signaling illuminated by genetically encoded molecular sensors and actuators.
Compartmentalized AMPK signaling illuminated by genetically encoded molecular sensors and actuators.
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DOI：
10.1016/j.celrep.2015.03.057
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发表时间：
2015-04-28
期刊：
影响因子：
8.8
通讯作者：
Inoue T
中科院分区：
文献类型：
--
作者：
Miyamoto T;Rho E;Sample V;Akano H;Magari M;Ueno T;Gorshkov K;Chen M;Tokumitsu H;Zhang J;Inoue T
AMP 激活蛋白激酶 (AMPK) 的活性是细胞活力的关键决定因素，在将细胞外和细胞内营养信息整合为调节各种代谢过程的信号方面发挥着基础作用。尽管 AMPK 很重要，但其在不同细胞内空间中的具体作用仍未解决，这很大程度上是由于缺乏实时、细胞器特异性 AMPK 活性探针。在这里，我们提出了一系列分子工具，可以测量不同亚细胞定位的 AMPK 活性，并可以快速诱导 AMPK 抑制。我们发现 AMPKα1（而不是 AMPKα2）是优先赋予 AMPK 空间特异性的亚基，并且抑制线粒体处的 AMPK 活性足以触发胞质 ATP 增加。这些发现表明，基因编码的分子探针代表了揭示 AMPK 调节时空性质基本原理的有力方法。
AMP-activated protein kinase (AMPK), whose activity is a critical determinant of cell vitality, serves a fundamental role in integrating extracellular and intracellular nutrient information into signals that regulate various metabolic processes. Despite the importance of AMPK, its specific roles within the different intracellular spaces remain unresolved, largely due to the lack of real-time, organelle-specific AMPK activity probes. Here, we present a series of molecular tools that allows for the measurement of AMPK activity at the different subcellular localizations and that allows for the rapid induction of AMPK inhibition. We discovered that AMPKα1, not AMPKα2, was the subunit that preferentially conferred spatial specificity to AMPK, and that inhibition of AMPK activity at the mitochondria was sufficient for triggering cytosolic ATP increase. These findings suggest that genetically encoded molecular probes represent a powerful approach for revealing the basic principles of the spatiotemporal nature of AMPK regulation.
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DOI：
10.1073/pnas.1009705107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Oakhill, Jonathan S.;Chen, Zhi-Ping;Kemp, Bruce E.
通讯作者：
Kemp, Bruce E.
影响因子：
9.2
作者：
Woods, A;Johnstone, SR;Carling, D
通讯作者：
Carling, D
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影响因子：
4
作者：
Mao, Luna;Li, Ning;Liu, Wei
通讯作者：
Liu, Wei
影响因子：
78.5
作者：
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通讯作者：
Shaw, Reuben J.
影响因子：
4.8
作者：
Miyamoto, Takafumi;Oshiro, Noriko;Yonezawa, Kazuyoshi
通讯作者：
Yonezawa, Kazuyoshi