对 AMPK 激活和功能的新见解,Nature Reviews Molecular Cell Biology

AMP 活化蛋白激酶 (AMPK) 的经典作用是作为一种细胞能量传感器，由下降的能量状态激活，由 AMP 与 ATP 和 ADP 与 ATP 比率的增加发出信号。一旦被激活，AMPK 通过促进产生 ATP 的分解代谢途径同时抑制能量消耗过程来恢复能量稳态。在这篇综述中，我们提供了关于这种典型（AMP/ADP 依赖性）激活机制的更新，但主要关注最近描述的非典型途径，包括 AMPK 感知葡萄糖、糖原或脂肪酸可用性的途径以及它感知溶酶体和核 DNA 的损伤。我们还讨论了关于碳水化合物和脂质代谢调节、线粒体和溶酶体稳态以及 DNA 修复的新发现。最后，我们讨论了 AMPK 在癌症、肥胖、糖尿病、

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The classical role of AMP-activated protein kinase (AMPK) is as a cellular energy sensor activated by falling energy status, signalled by increases in AMP to ATP and ADP to ATP ratios. Once activated, AMPK acts to restore energy homeostasis by promoting ATP-producing catabolic pathways while inhibiting energy-consuming processes. In this Review, we provide an update on this canonical (AMP/ADP-dependent) activation mechanism, but focus mainly on recently described non-canonical pathways, including those by which AMPK senses the availability of glucose, glycogen or fatty acids and by which it senses damage to lysosomes and nuclear DNA. We also discuss new findings on the regulation of carbohydrate and lipid metabolism, mitochondrial and lysosomal homeostasis, and DNA repair. Finally, we discuss the role of AMPK in cancer, obesity, diabetes, nonalcoholic steatohepatitis (NASH) and other disorders where therapeutic targeting may exert beneficial effects.