title: Zonated induction of autophagy and mitochondrial spheroids limits acetaminophen-induced necrosis in the liver.
abstract: 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 autophagy/mitophagy and the formation of mitochondrial spheroids.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, United States.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Ni
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Williams
authors.forename: Hartmut
authors.initials: H
authors.lastname: Jaeschke
authors.forename: Wen-Xing
authors.initials: WX
authors.lastname: Ding
mesh_terms: D000082:Acetaminophen; D000818:Animals; D001343:Autophagy; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018874:Spheroids, Cellular / Q000378:metabolism*
chemical_list: D000082:Acetaminophen
keywords: Acetaminophen; Autophagy; Liver injury; Mitochondrial spheroid; Mitophagy