Autophagy in ethanol-exposed liver disease

Abstract

Ethanol metabolism in hepatocytes causes the generation of reactive oxygen species, endoplasmic reticulum stress and alterations in mitochondrial energy and REDOX metabolism. In ethanol-exposed liver disease, autophagy not only acts as a cleanser to remove damaged organelles and cytosolic components, but also selectively clears specific targets such as lipid droplets and damaged mitochondria. Moreover, ethanol appears to play a role in protecting hepatocytes from apoptosis at certain concentrations. This article describes the evidence, function and potential mechanism of autophagy in ethanol-exposed liver disease and the controversy surrounding the effects of ethanol on autophagy.

Keywords:

• ethanol-induced autophagy
• hepatocyte
• liver disease
• selective autophagy

Financial & competing interests disclosure

The authors were supported by grants from the Scientific Research Foundation of Wenzhou, Zhejiang Province, China (H20090014, Y20090269), the Health Bureau of Zhejiang Province (2010KYB070), the Research Foundation of Education Bureau of Zhejiang Province (Y201009942) and the Project of New Century 551 Talent Nurturing in Wenzhou. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Alcoholic liver disease is a major cause of death worldwide.

• After acute ethanol treatment, the levels of LC3II (lipidated LC3) and lysosomal-associated membrane protein 1 increase which may support the premise that autophagy is a protective mechanism for ethanol-exposed hepatocytes.

• Ethanol-induced autophagy requires the metabolism of ethanol.

• In the early stages of ethanol-induced liver disease, endoplasmic reticulum stress can induce autophagy but in later stages of disease, endoplasmic reticulum stress may suppress autophagy.

• Autophagy is a selective process to clear unfolded proteins and damaged organelles.

• The results of acute and chronic ethanol exposure are determined not only by autophagic markers but also by the nuclear content of transcription factor EB.

• Recent studies reveal that the autophagic pathway is complex and further research is warranted.

Notes