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Biomolecules 2015, 5(4), 2619-2642; doi:10.3390/biom5042619

A Mechanistic Review of Mitophagy and Its Role in Protection against Alcoholic Liver Disease

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA
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Author to whom correspondence should be addressed.
Academic Editors: Natalia Osna and Kusum Kharbanda
Received: 11 July 2015 / Revised: 23 September 2015 / Accepted: 25 September 2015 / Published: 16 October 2015
(This article belongs to the Collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)
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Abstract

Alcoholic liver disease (ALD) is a major health problem worldwide, and alcohol is well-known to cause mitochondrial damage, which exacerbates alcohol-induced liver injury and steatosis. No successful treatments are currently available for treating ALD. Therefore, a better understanding of mechanisms involved in regulation of mitochondrial homeostasis in the liver and how these mechanisms may protect against alcohol-induced liver disease is needed for future development of better therapeutic options for ALD. Mitophagy is a key mechanism for maintaining mitochondrial homeostasis by removing damaged mitochondria, and mitophagy protects against alcohol-induced liver injury. Parkin, an E3 ubiquitin ligase, is well-known to induce mitophagy in in vitro models although Parkin-independent mechanisms for mitophagy induction also exist. In this review, we discuss the roles of Parkin and mitophagy in protection against alcohol-induced liver injury and steatosis. We also discuss Parkin-independent mechanisms for mitophagy induction, which have not yet been evaluated in the liver but may also potentially have a protective role against ALD. In addition to mitophagy, mitochondrial spheroid formation may also provide a novel mechanism of protection against ALD, but the role of mitochondrial spheroids in protection against ALD progression needs to be further explored. Targeting removal of damaged mitochondria by mitophagy or inducing formation of mitochondrial spheroids may be promising therapeutic options for treatment of ALD. View Full-Text
Keywords: alcohol; mitochondria; mitophagy; autophagy; Parkin; liver injury alcohol; mitochondria; mitophagy; autophagy; Parkin; liver injury
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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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Williams, J.A.; Ding, W.-X. A Mechanistic Review of Mitophagy and Its Role in Protection against Alcoholic Liver Disease. Biomolecules 2015, 5, 2619-2642.

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