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2篇 您的检索式:作者名="D. Grahame Hardie"
    题名 作者 年代 出处 被引量
1Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress显示文摘AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets. Low glucose activates AMPK exclusively through the AMP-independent, AXIN-based pathway in lysosomes to phosphorylate targets such as ACC1 and SREBP1c, exerting early anti-anabolic and pro-catabolic roles. Moderate increases in AMP expand this to activate cytosolic AMPK also in an AXIN-dependent manner. In contrast, high concentrations of AMP, arising from severe nutrient stress, activate all pools of AMPK independently of AXIN. Surprisingly, mitochondrion-localized AMPK is activated to phosphorylate ACC2 and mitochondrial fission factor (MFF) only during severe nutrient stress. Our findings reveal a spatiotemporal basis for hierarchical activation of different pools of AMPK during differing degrees of stress severity.Yue Zong Chen-Song Zhang Mengqi Li Wen Wang Zhichao Wang Simon A. Hawley Teng Ma Jin-Wei Feng Xiao Tian Qu Qi Yu-Qing Wu Cixiong Zhang Zhiyun Ye Shu-Yong Lin Hai-Long Piao D. Grahame Hardie Sheng-Cai Lin 2019Cell Research2019,29,6:8
2Age-related HMG-CoA reductase deregulation depends on ROS-induced p38 activation显示文摘Valentina Pallottini Chiara Martini Gabriella Cavallini Ettore Bergamini Kirsty J. Mustard D. Grahame Hardie Anna Trentalance 2007Mechanisms of Ageing and Development2007,,11:1
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