Acyl-CoA synthetase 5 induces apoptosis sensitisation in human hepatocytes by channelling Acyl-CoAs into sphingolipid metabolism

In the pathogenesis of nonalcoholic fatty liver disease, accumulation of lipids in hepatocytes and hepatocyte apoptosis are strongly implicated in disease progression from the potentially reversible condition of steatosis to severe acute and chronic liver injury. Acyl-CoA synthetase 5 (ACSL5), a member of the ACSL gene family that catalyzes the activation of long-chain fatty acids for lipid biosynthesis, is the only ACSL isoform located on mitochondria and involved in apoptosis. Up-regulation of ACSL5 by fatty acids is found to increase apoptosis susceptibility in human hepatocytes and thus was hypothesized to b…