AMP-激活蛋白激酶（AMPK）的经典作用是作为细胞能量传感器，通过增加AMP/ATP和ADP/ATP比例的信号来激活。一旦激活，AMPK通过促进产生ATP的分解代谢途径并抑制能量消耗过程来恢复能量稳态。在本综述中，我们对这种经典（AMP/ADP依赖性）激活机制进行更新，但主要关注最近描述的非经典途径，包括AMPK感知葡萄糖、糖原或脂肪酸可用性的途径，以及AMPK感知溶酶体和核DNA损伤的途径。我们还讨论了关于碳水化合物和脂质代谢、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、非酒精性脂肪性肝病（NASH）和其他疾病中的作用，其中治疗靶向可能产生益处。© 2022.Springer Nature Limited.

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.© 2022. Springer Nature Limited.