The mTORC1-G9a-H3K9me2 axis negatively regulates autophagy in fatty acid-induced hepatocellular lipotoxicity.

ABSTRACT: Defective autophagy and lipotoxicity are the hallmarks of nonalcoholic fatty liver disease. However, the precise molecular mechanism for the defective autophagy in lipotoxic conditions is not fully known. In the current study, we elucidated that activation of the mammalian target of rapamycin complex 1 (mTORC1)-G9a-H3K9me2 axis in fatty acid-induced lipotoxicity blocks autophagy by repressing key autophagy genes. The fatty acid-treated cells show mTORC1 activation, increased histone methyltransferase G9a levels, and suppressed autophagy as indicated by increased accumulation of the key autophagic cargo SQSTM1/p62 and decreased levels of autophagy-related proteins LC3II, Beclin1, and Atg7. Our chromatin immunoprecipitation analysis showed that decrease in autophagy was associated with incre

SUBMITTER: Mushtaq A 

PROVIDER: S-EPMC9957777 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature