Disruption of the vacuolar-type H⁺-ATPase complex in liver causes MTORC1-independent accumulation of autophagic vacuoles and lysosomes.

ABSTRACT: The vacuolar-type H⁺-translocating ATPase (v-H⁺-ATPase) has been implicated in the amino acid-dependent activation of the mechanistic target of rapamycin complex 1 (MTORC1), an important regulator of macroautophagy. To reveal the mechanistic links between the v-H⁺-ATPase and MTORC1, we destablilized v-H⁺-ATPase complexes in mouse liver cells by induced deletion of the essential chaperone ATP6AP2. ATP6AP2-mutants are characterized by massive accumulation of endocytic and autophagic vacuoles in hepatocytes. This cellular phenotype was not caused by a block in endocytic maturation or an impaired acidification. However, the degradation of LC3-II in the knockout hepatocytes appeared to be reduced. When v-H⁺-ATPase levels were decreased, we

SUBMITTER: Kissing S 

PROVIDER: S-EPMC5388235 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature