代谢稳态和将能量供应与需求联系起来的能力是所有活细胞生长和增殖的基本要求。所有真核生物代谢稳态的关键是 AMPK 和 mTORC1，这两种激酶可感知营养水平并作为分解代谢 (AMPK) 和合成代谢 (mTORC1) 的抵消调节因子来控制细胞存活、生长和增殖。 2000 年代初期开始的发现表明，AMPK 和 mTORC1 通过直接和间接磷酸化事件进行通信或串扰，以调节彼此及其共享蛋白底物 ULK1（自噬的主要启动子）的活性，从而使细胞代谢快速进行。适应能量和营养状态。最近的报告描述了 AMPK/mTORC1 串扰的不同机制以及 AMPK 和 mTORC1 在溶酶体中激活的复杂方式。在这里，我们对这一令人兴奋的领域的当前理解进行了全面概述，并对新证据进行了评论，这些新证据表明 mTORC1 反馈延伸到 AMPK 同工型水平，这对于某些特定 AMPK 同工型与疾病发病机制有关的癌症特别相关。© 2024作者。

Metabolic homeostasis and the ability to link energy supply to demand are essential requirements for all living cells to grow and proliferate. Key to metabolic homeostasis in all eukaryotes are AMPK and mTORC1, two kinases that sense nutrient levels and function as counteracting regulators of catabolism (AMPK) and anabolism (mTORC1) to control cell survival, growth and proliferation. Discoveries beginning in the early 2000s revealed that AMPK and mTORC1 communicate, or cross-talk, through direct and indirect phosphorylation events to regulate the activities of each other and their shared protein substrate ULK1, the master initiator of autophagy, thereby allowing cellular metabolism to rapidly adapt to energy and nutritional state. More recent reports describe divergent mechanisms of AMPK/mTORC1 cross-talk and the elaborate means by which AMPK and mTORC1 are activated at the lysosome. Here, we provide a comprehensive overview of current understanding in this exciting area and comment on new evidence showing mTORC1 feedback extends to the level of the AMPK isoform, which is particularly pertinent for some cancers where specific AMPK isoforms are implicated in disease pathogenesis.© 2024 The Author(s).