Peripheral lysosome levels dictate mTORC1 inactivation even when catabolically impaired.

ABSTRACT: The mechanistic target of rapamycin complex 1 (mTORC1) is a central driver of cell growth that is frequently hyperactivated in cancer. While mTORC1 is activated at the lysosomal surface in response to growth factors and amino acids, the processes governing its inactivation are not fully understood. Here, we report that sustained mTORC1 suppression during leucine or arginine starvation requires the translocation of peripheral lysosomes to the perinuclear region. Our data suggest that a pool of mTOR remains active at peripheral lysosomes during starvation, and that increased spatial separation between lysosomes and the plasma membrane attenuates PI3K/Akt signaling-thereby reducing inputs that otherwise maintain mTORC1 activity. Consequently, preventing lysosome translocation and increasing p

SUBMITTER: Dang HQ 

PROVIDER: S-EPMC12849086 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature