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World J Gastroenterol. Oct 7, 2007; 13(37): 4967-4973
Published online Oct 7, 2007. doi: 10.3748/wjg.v13.i37.4967
Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease
Sudheer K Mantena, Adrienne L King, Kelly K Andringa, Aimee Landar, Victor Darley-Usmar, Shannon M Bailey
Sudheer K Mantena, Adrienne L King, Kelly K Andringa, Shannon M Bailey, Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, United States
Aimee Landar, Victor Darley-Usmar, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States
Author contributions: All authors contributed equally to the work.
Supported by NIH/NIAAA grants AA13395 (VDU) and AA15172 (SMB)
Correspondence to: Shannon M Bailey, Department of Environmental Health Sciences, Center for Free Radical Biology, University of Alabama at Birmingham, Ryals Building, Room 623,1530 3rd Avenue South, Birmingham, AL 35294, United States. sbailey@uab.edu
Telephone: +1-205-9347070 Fax: +1-205-9756341
Received: June 30, 2007
Revised: July 18, 2007
Accepted: July 26, 2007
Published online: October 7, 2007
Abstract

Mitochondrial dysfunction is known to be a contributing factor to a number of diseases including chronic alcohol induced liver injury. While there is a detailed understanding of the metabolic pathways and proteins of the liver mitochondrion, little is known regarding how changes in the mitochondrial proteome may contribute to the development of hepatic pathologies. Emerging evidence indicates that reactive oxygen and nitrogen species disrupt mitochondrial function through post-translational modifications to the mitochondrial proteome. Indeed, various new affinity labeling reagents are available to test the hypothesis that post-translational modification of proteins by reactive species contributes to mitochondrial dysfunction and alcoholic fatty liver disease. Specialized proteomic techniques are also now available, which allow for identification of defects in the assembly of multi-protein complexes in mitochondria and the resolution of the highly hydrophobic proteins of the inner membrane. In this review knowledge gained from the study of changes to the mitochondrial proteome in alcoholic hepatotoxicity will be described and placed into a mechanistic framework to increase understanding of the role of mitochondrial dysfunction in liver disease.

Keywords: Mitochondria; Alcohol; Liver; Oxidative stress; Nitric oxide; Proteomics; Post-translational modifications