Lysine acetylation induced by chronic ethanol consumption impairs dynamin-mediated clathrin-coated vesicle release

Blythe D. Shepard, Dean J. Tuma, Pamela L. Tuma

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The liver is the major site of ethanol metabolism and thus sustains the most injury from chronic alcohol consumption. Ethanol metabolism by the hepatocyte leads to the generation of reactive metabolites and oxygen radicals that can readily adduct DNA, lipids, and proteins. More recently, it has become apparent that ethanol consumption also leads to increased post-translational modifications of the natural repertoire, including lysine hyperacetylation. Previously, we determined that alcohol consumption selectively impairs clathrin-mediated internalization in polarized hepatocytes. However, neither the step at which the block occurs nor the mechanism responsible for the defect have been identified. To identify the specific step at which clathrin-mediated internalization is impaired, we examined the distributions, levels, and assembly of selected components of the clathrin machinery in control and ethanol-treated cells. To determine whether the impairment is caused by ethanol-induced lysine acetylation, we also examined the same coat components in cells treated with trichostatin A (TSA), a deacetylase inhibitor that leads to protein hyperacetylation in the absence of ethanol. Conclusion: We determined that both ethanol and TSA impair internalization at a late stage before vesicle fission. We further determined that this defect is likely the result of decreased dynamin recruitment to the necks of clathrin-coated invaginations resulting in impaired vesicle budding. These results also raise the exciting possibility that agents that promote lysine deacetylation may be effective therapeutics for the treatment of alcoholic liver disease.

Original languageEnglish (US)
Pages (from-to)1260-1270
Number of pages11
JournalHepatology
Volume55
Issue number4
DOIs
StatePublished - Apr 1 2012

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Clathrin-Coated Vesicles
Dynamins
Acetylation
Lysine
Ethanol
Clathrin
trichostatin A
Alcohol Drinking
Hepatocytes
Alcoholic Liver Diseases
DNA Adducts
Cellular Structures
Post Translational Protein Processing
Reactive Oxygen Species
Proteins
Neck
Lipids
Liver
Wounds and Injuries

ASJC Scopus subject areas

  • Hepatology

Cite this

Lysine acetylation induced by chronic ethanol consumption impairs dynamin-mediated clathrin-coated vesicle release. / Shepard, Blythe D.; Tuma, Dean J.; Tuma, Pamela L.

In: Hepatology, Vol. 55, No. 4, 01.04.2012, p. 1260-1270.

Research output: Contribution to journalArticle

Shepard, Blythe D. ; Tuma, Dean J. ; Tuma, Pamela L. / Lysine acetylation induced by chronic ethanol consumption impairs dynamin-mediated clathrin-coated vesicle release. In: Hepatology. 2012 ; Vol. 55, No. 4. pp. 1260-1270.
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