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Biomolecules 2015, 5(3), 2140-2159; doi:10.3390/biom5032140

The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

Department of Biology, The Catholic University of America, Washington, DC 20064, USA
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Author to whom correspondence should be addressed.
Academic Editors: Natalia Osna and Kusum Kharbanda
Received: 22 July 2015 / Revised: 21 August 2015 / Accepted: 24 August 2015 / Published: 18 September 2015
(This article belongs to the Collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)

Abstract

The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.
Keywords: microtubules; tubulin; acetylation; post-translational modifications; ethanol; hepatocytes; liver microtubules; tubulin; acetylation; post-translational modifications; ethanol; hepatocytes; liver
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Groebner, J.L.; Tuma, P.L. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease. Biomolecules 2015, 5, 2140-2159.

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