mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction.

Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that is active in nearly all proliferating eukaryotic cells; however, it is unclear whether mTORC1 activity changes throughout the cell cycle. We find that mTORC1 activity oscillates from lowest in mitosis/G1 to highest in S/G2. The interphase oscillation is mediated through the TSC complex but is independent of major known regulatory inputs, including Akt and Mek/Erk signaling. By contrast, suppression of mTORC1 activity in mitosis does not require the TSC complex. mTORC1 has long been known to promote progression through G1. We find that mTORC1 also promotes progression through S and G2 and is important for satisfying the Chk1/Wee1-dependent G2/M checkpoint to allow entry into mitosis. We also find that low mTORC1 activity in G1 sensitizes cells to autophagy induction in response to partial mTORC1 inhibition or reduced nutrient levels. Together, these findings demonstrate that mTORC1 is differentially regulated throughout the cell cycle, with important phase-specific consequences for proliferating cells. [Display omitted] • mTORC1 activity oscillates throughout the cell cycle, peaking in S/G2 and low in M/G1 • The interphase oscillation in mTORC1 activity is mediated through the TSC complex • mTORC1 promotes progression through G1, S, and G2 but not mitosis • Low mTORC1 activity in G1 sensitizes cells to induction of autophagy mTORC1 is a master metabolic regulator that stimulates anabolic cell growth and proliferation and suppresses catabolic processes such as autophagy. Joshi et al. find that mTORC1 activity oscillates throughout the cell cycle, promoting progression through interphase and entry into mitosis and resulting in differential sensitivity to autophagy induction. [ABSTRACT FROM AUTHOR]