Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatotoxicity
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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.
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Oxidative modification and suppression of ALDH2 in alcohol-exposed rodents were consistently observed by other groups.
“Oxidative modification and suppression of ALDH2 in alcohol-exposed rodents were consistently observed by other groups [44], [45].”
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“sistently observed by other groups [44,45].”
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Self-citation
- Authors
- Venkatraman, A., Landar, A., Davis, A. J., Chamlee, L., Sanderson, T., Kim, H., Page, G., Pompilius, M., Ballinger, S., Darley-Usmar, V., & Bailey, S. M.
- Affiliations
- University of Alabama (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Bailey, Shannon M.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 279
- Issue
- 21
- Pages
- 22092-22101
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2039579730
- Cited by
- 170
- References
- 65
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 9 · 2012: 15
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (13395, 13682)
- National Cancer Institute (P30CA013148)
- National Center for Research Resources (S10RR016849, S10RR011329)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- mitochondrial proteome, chronic ethanol exposure, ethanol-induced hepatotoxicity, oxidative phosphorylation complexes, mitochondrial DNA damage, reactive oxygen species, oxidative stress, mitochondrial protein expression, stress response
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Cell Nucleus, DNA Damage, DNA, Mitochondrial, Electrophoresis, Polyacrylamide Gel, Isoelectric Focusing, Liver, Male, Mitochondria, Mitochondria, Liver, Oxygen, Phosphorylation, Electrophoresis, Gel, Two-Dimensional, Rats, Sprague-Dawley, Reactive Oxygen Species, Proteome, Reactive Nitrogen Species, Rats
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