AMPK的缺氧激活依赖于线粒体活性氧，但不依赖于AMP/ATP比值的增加。
Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio.
作者信息
Emerling Brooke M, Weinberg Frank, Snyder Colleen, Burgess Zach, Mutlu Gökhan M, Viollet Benoit, Budinger G R Scott, Chandel Navdeep S
机构信息
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
出版信息
Free Radic Biol Med. 2009 May 15;46(10):1386-91. doi: 10.1016/j.freeradbiomed.2009.02.019. Epub 2009 Mar 3.
AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in metazoans that is known to be activated by stimuli that increase the cellular AMP/ATP ratio. Full activation of AMPK requires specific phosphorylation within the activation loop of the catalytic domain of the alpha-subunit by upstream kinases such as the serine/threonine protein kinase LKB1. Here we show that hypoxia activates AMPK through LKB1 without an increase in the AMP/ATP ratio. Hypoxia increased reactive oxygen species (ROS) levels and the antioxidant EUK-134 abolished the hypoxic activation of AMPK. Cells deficient in mitochondrial DNA (rho(0) cells) failed to activate AMPK during hypoxia but are able to in the presence of exogenous H(2)O(2). Furthermore, we provide genetic evidence that ROS generated within the mitochondrial electron transport chain and not oxidative phosphorylation is required for hypoxic activation of AMPK. Collectively, these data indicate that oxidative stress and not an increase in the AMP/ATP ratio is required for hypoxic activation of AMPK.
AMP激活的蛋白激酶（AMPK）是后生动物中发现的一种细胞能量状态传感器，已知其可被增加细胞AMP/ATP比值的刺激所激活。AMPK的完全激活需要上游激酶（如丝氨酸/苏氨酸蛋白激酶LKB1）在α亚基催化结构域的激活环内进行特定的磷酸化。在此我们表明，缺氧通过LKB1激活AMPK，而不增加AMP/ATP比值。缺氧增加了活性氧（ROS）水平，抗氧化剂EUK-134消除了AMPK的缺氧激活。线粒体DNA缺陷细胞（ρ⁰细胞）在缺氧期间未能激活AMPK，但在存在外源性H₂O₂时能够激活。此外，我们提供了遗传学证据，表明线粒体电子传递链内产生的ROS而非氧化磷酸化是AMPK缺氧激活所必需的。总体而言，这些数据表明，AMPK缺氧激活需要氧化应激而非AMP/ATP比值的增加。
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