Direct control of lysosomal catabolic activity by mTORC1 through regulation of V-ATPase assembly.

ABSTRACT: Mammalian cells can acquire exogenous amino acids through endocytosis and lysosomal catabolism of extracellular proteins. In amino acid-replete environments, nutritional utilization of extracellular proteins is suppressed by the amino acid sensor mechanistic target of rapamycin complex 1 (mTORC1) through an unknown process. Here, we show that mTORC1 blocks lysosomal degradation of extracellular proteins by suppressing V-ATPase-mediated acidification of lysosomes. When mTORC1 is active, peripheral V-ATPase V₁ domains reside in the cytosol where they are stabilized by association with the chaperonin TRiC. Consequently, most lysosomes display low catabolic activity. When mTORC1 activity declines, V-ATPase V₁ domains move to membrane-integral V-ATPase V_o domain

SUBMITTER: Ratto E 

PROVIDER: S-EPMC9385660 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature