Zonated induction of autophagy and mitochondrial spheroids limits acetaminophen-induced necrosis in the liver

Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the US and many western countries, It is well known that APAP induces mitochondrial damage to trigger centrilobular necrosis. Emerging evidence suggests that autophagic removal of damaged mitochondria may protect against APAP-induced liver injury. Electron and confocal microscopy analysis of liver tissues revealed that APAP overdose triggers unique biochemical and pathological zonated changes in the mouse liver, which includes necrosis (zone 1), mitochondrial spheroid formation (zone 2), autophagy (zone 3) and mitochondrial biogenesis (zone 4). In this graphic review, we discuss the role of autophagy/mitophagy in limiting the expansion of necrosis and promoting mitochondrial biogenesis and liver regeneration for the recovery of APAP-induced liver injury. We also discuss possible mechanisms that could be involved in regulating APAP-induced autophagylmitophagy and the formation of mitochondrial spheroids. (C) 2013 The Authors. Published by Elsevier B.V. Open access under CC BY-NC-ND license.