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Redox Biol. 2013 Aug 26;1:427-32. doi: 10.1016/j.redox.2013.08.005.

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

Author information

1
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, United States.

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.

KEYWORDS:

Acetaminophen; Autophagy; Liver injury; Mitochondrial spheroid; Mitophagy

PMID:
24191236
PMCID:
PMC3814950
DOI:
10.1016/j.redox.2013.08.005
[Indexed for MEDLINE]
Free PMC Article

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