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Review
. 2020 Apr 22:6:27.
doi: 10.1038/s41420-020-0260-9. eCollection 2020.

How does mTOR sense glucose starvation? AMPK is the usual suspect

Gabriel Leprivier  1 , Barak Rotblat  2
Affiliations
Review

How does mTOR sense glucose starvation? AMPK is the usual suspect

Gabriel Leprivier et al. Cell Death Discov. .

Abstract

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.

Keywords: Cell biology; Cell signalling.

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Conflict of interest statement

Conflict of interestThe authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. AMPK, Rag GTPases, GADD34, and TBC1D7 regulation of mTORC1 in response to glucose levels.
Orange corresponds to active molecules; gray corresponds to inactive molecules.
Fig. 2
Fig. 2. ULK1 and LARS regulate mTORC1 in a glucose-dependent manner.
Orange corresponds to active molecules; gray corresponds to inactive molecules.
Fig. 3
Fig. 3. PFKFB3 and HK2 pathways control mTORC1 in response to glucose concentrations.
F-6-P is fructose 6-P; F-2,6-bisP is fructose 2,6-P2. Orange corresponds to active molecules; gray corresponds to inactive molecules.
See this image and copyright information in PMC

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