AMPK and TOR: the Yin and Yang of Cellular Nutrient Sensing and Growth Control
Authors: Asier González, Michael N. Hall, Sheng-Cai Lin, D.Grahame Hardie
Abstract: 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.