Signal integration by mTORC1 coordinates nutrient input with biosynthetic output

摘要

Flux through metabolic pathways is inherently sensitive to the levels of specific substrates and products, but cellular metabolismis also managed by integrated control mechanisms that sense the nutrient and energy status of a cell or organism. The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a protein kinase complex ubiquitous to eukaryotic cells, has emerged as a critical signaling node that links nutrient sensing to the coordinated regulation of cellular metabolism. Here, the role of mTORC1 as a conduit between cellular growth conditions and the anabolic processes that promote cell growth is discussed. The emerging network of signaling pathways by which mTORC1 integrates systemic signals, in the form of secreted growth factors, with local signals, in the form of cellular nutrients (amino acids, glucose, and oxygen) and energy (ATP) is detailed. Our expanding understanding of the exquisite regulatory network upstream of mTORC1 provides molecular insights into the integrated sensing mechanisms by which diverse cellular signals converge to control cell physiology.