Mitochondrial GpC and CpG DNA Hypermethylation Cause Metabolic Stress-Induced Mitophagy and Cholestophagy.

ABSTRACT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by a constant accumulation of lipids in the liver. This hepatic lipotoxicity is associated with a dysregulation of the first step in lipid catabolism, known as beta oxidation, which occurs in the mitochondrial matrix. Eventually, this dysregulation will lead to mitochondrial dysfunction. To evaluate the possible involvement of mitochondrial DNA methylation in this lipid metabolic dysfunction, we investigated the functional metabolic effects of mitochondrial overexpression of CpG (MSssI) and GpC (MCviPI) DNA methyltransferases in relation to gene expression and (mito)epigenetic signatures. Overall, the results show that mitochondrial GpC and, to a lesser extent, CpG methylation increase bile acid metabolic gen

SUBMITTER: Theys C 

PROVIDER: S-EPMC10671279 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature