Apoptosis sensitization of hepatocytes by acyl-CoA synthetase 5 involves deregulation of sphingolipid metabolism and alterations in mitochondrial signalling

Fatty acid accumulation in hepatocytes and subsequent hepatocyte lipoapoptosis are key features in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and associated acute and chronic liver injury. The initial step in fatty acid and lipid metabolism is the activation of fatty acids catalyzed by long chain acyl-CoA synthetases (ACSL). ACSL5, a mitochondrially located isoform that is upregulated in hepatic steatosis has been revealed to increase hepatocellular apoptosis susceptibility. In this study, we investigated the molecular mechanisms selectively sensitizing hepatocytes to apoptosis by ACSL5. Using…