AMPK and TOR: the Yin and Yang of cellular nutrient sensing and growth control

TY - JOUR

T1 - AMPK and TOR

T2 - the Yin and Yang of cellular nutrient sensing and growth control

AU - González, Asier

AU - Hall, Michael N.

AU - Lin, Sheng-Cai

AU - Hardie, D. Grahame

N1 - M.N.H. acknowledges support from the European Research Council (MERiC, 609883), the Louis Jeantet Foundation, and the Swiss National Science Foundation (310030B-179569). S.C.L. acknowledges supports from the National Natural Science Foundation of China (#31730058, #31430094, #31601152 and #31690101) and the National Key R&D Program of China (2016YFA0502001). D.G.H. acknowledges support from an Investigator Award from the Wellcome Trust (204766). Invited review article.

PY - 2020/3/3

Y1 - 2020/3/3

N2 - The AMPK (AMP-activated protein kinase) and TOR (target-of-rapamycin) pathways are interlinked, opposing signaling pathways involved in sensing availability of nutrients and energy and regulation of cell growth. AMPK (Yin, or the “dark side”) is switched on by lack of energy or nutrients and inhibits cell growth, while TOR (Yang, or the “bright side”) is switched on by nutrient availability and promotes cell growth. Genes encoding the AMPK and TOR complexes are found in almost all eukaryotes, suggesting that these pathways arose very early during eukaryotic evolution. During the development of multicellularity, an additional tier of cell-extrinsic growth control arose that is mediated by growth factors, but these often act by modulating nutrient uptake so that AMPK and TOR remain the underlying regulators of cellular growth control. In this review, we discuss the evolution, structure, and regulation of the AMPK and TOR pathways and the complex mechanisms by which they interact.

AB - The AMPK (AMP-activated protein kinase) and TOR (target-of-rapamycin) pathways are interlinked, opposing signaling pathways involved in sensing availability of nutrients and energy and regulation of cell growth. AMPK (Yin, or the “dark side”) is switched on by lack of energy or nutrients and inhibits cell growth, while TOR (Yang, or the “bright side”) is switched on by nutrient availability and promotes cell growth. Genes encoding the AMPK and TOR complexes are found in almost all eukaryotes, suggesting that these pathways arose very early during eukaryotic evolution. During the development of multicellularity, an additional tier of cell-extrinsic growth control arose that is mediated by growth factors, but these often act by modulating nutrient uptake so that AMPK and TOR remain the underlying regulators of cellular growth control. In this review, we discuss the evolution, structure, and regulation of the AMPK and TOR pathways and the complex mechanisms by which they interact.

UR - https://www.scopus.com/pages/publications/85080047511

U2 - 10.1016/j.cmet.2020.01.015

DO - 10.1016/j.cmet.2020.01.015

M3 - Review article

C2 - 32130880

SN - 1550-4131

VL - 31

SP - 472

EP - 492

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -