Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.

细胞不断调整其新陈代谢，以满足其能量需求并对营养物质的利用作出反应。真核生物已经进化出一种非常复杂的系统，可以通过丝氨酸/苏氨酸激酶AMP激活的蛋白激酶（AMPK）复合体来检测低水平的细胞ATP。在低能量的条件下，AMPK使特定的酶和生长控制节点磷酸化，从而增加ATP的产生并减少ATP的消耗。在过去的十年中，发现了许多新的AMPK底物，使人们对将细胞代谢从合成代谢重新编程为分解代谢所需的最少步骤有了更全面的了解。这种能量开关控制细胞的生长和其他几个细胞过程，包括脂质和葡萄糖的代谢以及自噬。最近的研究表明，AMPK的一项祖先功能是促进线粒体健康，而AMPK的多个新发现的靶标涉及线粒体稳态的各个方面，包括线粒体吞噬。这篇评论讨论了AMPK如何作为细胞对高能应激和线粒体损伤的反应的中心介质，并协调自噬和线粒体生物学的多种特征。