title: Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatotoxicity.
abstract: Mitochondria are particularly susceptible to increased formation of reactive oxygen and nitrogen species in the cell that can occur in response to pathological and xenobiotic stimuli. Proteomics can give insights into both mechanism of pathology and adaptation to stress. Herein we report the use of proteomics to evaluate alterations in the levels of mitochondrial proteins following chronic ethanol exposure in an animal model. Forty-three proteins showed differential expression, 13 increased and 30 decreased, as a consequence of chronic ethanol. Of these proteins, 25 were not previously known to be affected by chronic ethanol emphasizing the power of proteomic approaches in revealing global responses to stress. Both nuclear and mitochondrially encoded gene products of the oxidative phosphorylation complexes in mitochondria from ethanol-fed rats were decreased suggesting an assembly defect in this integrated metabolic pathway. Moreover mtDNA damage was increased by ethanol demonstrating that the effects of ethanol consumption extend beyond the proteome to encompass mtDNA. Taken together, we have demonstrated that chronic ethanol consumption extends to a modification of the mitochondrial proteome far broader than realized previously. These data also suggest that the response of mitochondria to stress may not involve non-discriminate changes in the proteome but is restricted to those metabolic pathways that have a direct role in a specific pathology.
authors.affiliation: Department of Pathology, University of Alabama, Birmingham, Alabama 35294, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Venkatraman
authors.forename: Aimee
authors.initials: A
authors.lastname: Landar
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Davis
authors.forename: Laura
authors.initials: L
authors.lastname: Chamlee
authors.forename: Todd
authors.initials: T
authors.lastname: Sanderson
authors.forename: Helen
authors.initials: H
authors.lastname: Kim
authors.forename: Grier
authors.initials: G
authors.lastname: Page
authors.forename: Melissa
authors.initials: M
authors.lastname: Pompilius
authors.forename: Scott
authors.initials: S
authors.lastname: Ballinger
authors.forename: Victor
authors.initials: V
authors.lastname: Darley-Usmar
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Bailey
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D000431:Ethanol / Q000494:pharmacology / Q000633:toxicity*; D007525:Isoelectric Focusing; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D020543:Proteome; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
chemical_list: D004272:DNA, Mitochondrial; D020543:Proteome; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000431:Ethanol; D010100:Oxygen