How does mTOR sense glucose starvation? AMPK is the usual suspect.,Cell Death Discovery

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How does mTOR sense glucose starvation? AMPK is the usual suspect.
Cell Death Discovery ( IF 6.1 ) Pub Date : 2020-04-22 , DOI: 10.1038/s41420-020-0260-9
Gabriel Leprivier ₁ , Barak Rotblat ₂

Affiliation

Glucose is a major requirement for biological life. Its concentration is constantly sensed at the cellular level, allowing for adequate responses to any changes of glucose availability. Such responses are mediated by key sensors and signaling pathway components that adapt cellular metabolism to glucose levels. One of the major hubs of these responses is mechanistic target of rapamycin (mTOR) kinase, which forms the mTORC1 and mTORC2 protein complexes. Under physiological glucose concentrations, mTORC1 is activated and stimulates a number of proteins and enzymes involved in anabolic processes, while restricting the autophagic process. Conversely, when glucose levels are low, mTORC1 is inhibited, in turn leading to the repression of numerous anabolic processes, sparing ATP and antioxidants. Understanding how mTORC1 activity is regulated by glucose is not only important to better delineate the biological function of mTOR, but also to highlight potential therapeutic strategies for treating diseases characterized by deregulated glucose availability, as is the case of cancer. In this perspective, we depict the different sensors and upstream proteins responsible of controlling mTORC1 activity in response to changes in glucose concentration. This includes the major energy sensor AMP-activated protein kinase (AMPK), as well as other independent players. The impact of such modes of regulation of mTORC1 on cellular processes is also discussed.

中文翻译：

mTOR 如何感知葡萄糖饥饿？AMPK 是最常见的嫌疑人。

葡萄糖是生物生命的主要需求。它的浓度在细胞水平上不断被感知，从而能够对葡萄糖可用性的任何变化做出充分的反应。这种反应是由关键传感器和信号通路成分介导的，这些传感器和信号通路成分使细胞代谢适应葡萄糖水平。这些反应的主要中心之一是雷帕霉素 (mTOR) 激酶的机制靶标，它形成 mTORC1 和 mTORC2 蛋白复合物。在生理葡萄糖浓度下，mTORC1 被激活并刺激许多参与合成代谢过程的蛋白质和酶，同时限制自噬过程。相反，当葡萄糖水平较低时，mTORC1 会受到抑制，进而导致众多合成代谢过程受到抑制，从而节省 ATP 和抗氧化剂。了解 mTORC1 活性如何受葡萄糖调节不仅对于更好地描述 mTOR 的生物学功能很重要，而且还可以强调治疗以葡萄糖可用性失调为特征的疾病（如癌症）的潜在治疗策略。从这个角度来看，我们描述了负责控制 mTORC1 活性以响应葡萄糖浓度变化的不同传感器和上游蛋白质。这包括主要的能量传感器 AMP 激活蛋白激酶 (AMPK) 以及其他独立参与者。还讨论了 mTORC1 的这种调节模式对细胞过程的影响。

更新日期：2020-04-24

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