An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis

Liver disease defect identified The energy sensor adenosine monophosphate–activated protein kinase (AMPK) is implicated in liver damage in nonalcoholic steatohepatitis (NASH), a leading cause of liver-associated death in humans. Zhao et al. used mouse models of NASH and samples from human NASH patients to show that AMPK, the activity of which is lost in NASH, phosphorylates the enzyme procaspase-6. In normal liver cells, this modification limits the activation of caspase-6 and the consequent caspase activation cascade that leads to apoptosis. AMPK and caspase-6 may thus provide therapeutic targets for the treatment of NASH. Science , this issue p. 652