mTOR-Dependent Cell Survival Mechanisms

The mechanistic target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) (mTOR) kinase is a conserved regulator of cell growth, proliferation, and survival. In cells, mTOR is the catalytic subunit of two complexes called mTORC1 and mTORC2, which have distinct upstream regulatory signals and downstream substrates. mTORC1 directly senses cellular nutrient availability while indirectly sensing circulating nutrients through growth factor signaling pathways. Cellular stresses that restrict growth also impinge on mTORC1 activity. mTORC2 is less well understood and appears only to sense growth factors. As an integrator of diverse growth regulatory signals, mTOR evolved to be a central signaling hub for controlling cellular metabolism and energy homoeostasis, and defects in mTOR signaling are important in the pathologies of cancer, diabetes, and aging. Here we discuss mechanisms by which each mTOR complex might regulate cell survival in response to metabolic and other stresses.