Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications
Open accessAbstract
Aldehyde dehydrogenases (ALDHs) represent large family members of NAD(P)+-dependent dehydrogenases responsible for the irreversible metabolism of many endogenous and exogenous aldehydes to the corresponding acids. Among 19 ALDH isozymes, mitochondrial ALDH2 is a low Km enzyme responsible for the metabolism of acetaldehyde and lipid peroxides such as malondialdehyde and 4-hydroxynonenal, both of which are highly reactive and toxic. Consequently, inhibition of ALDH2 would lead to elevated levels of acetaldehyde and other reactive lipid peroxides following ethanol intake and/or exposure to toxic chemicals. In addition, many East Asian people with a dominant negative mutation in ALDH2 gene possess a decreased ALDH2 activity with increased risks for various types of cancer, myocardial infarct, alcoholic liver disease, and other pathological conditions. The aim of this review is to briefly describe the multiple post-translational modifications of mitochondrial ALDH2, as an example, after exposure to toxic chemicals or under different disease states and their pathophysiological roles in promoting alcohol/drug-mediated tissue damage. We also briefly mention exciting preclinical translational research opportunities to identify small molecule activators of ALDH2 and its isozymes as potentially therapeutic/preventive agents against various disease states where the expression or activity of ALDH enzymes is altered or inactivated.
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ALDH2 and other ALDH isozymes, which contain the highly conserved active site Cys residue, can be reversibly modulated by S-nitrosylation under increased nitroxidative stress.
“These results indicate that ALDH2 and other ALDH isozymes, which contain the highly conserved active site Cys residue, can be reversibly modulated by S-nitrosylation under increased nitroxidative stress, as reviewed [42].”
These phenomena could explain the decreased levels of ALDH2 activity in alcoholic individuals.
“In fact, these phenomena could explain the decreased levels of ALDH2 activity in alcoholic individuals, as discussed [34], [42].”
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ALDH2 plays a role in spermatogenesis and male fertility by regulating oxidative stress in mice
Lv, Y., Yang, X., Sun, X., Lv, L., Zhang, Z., Li, C., Gao, J., Li, H., Wen, Z., & Zhu, H. (2024) · Experimental Cell Research · doi:10.1016/j.yexcr.2024.114397 · Cited by 2 · see citing works
THE NRF-1/GABP/BRCA1 Transcriptional Network in Mammary Epithelial Differentiation
Thompson, C. (2012) · QSpace (Queen's University Library) · Cited by 1 · see citing works
Evaluation of Cardiac Mitochondrial Function in the Fructose-Fed Rat
Scott, K. Y. (2016) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3r20s218
Associação entre a expressão e a função da enzima ALDH1 no câncer de mama
Mandarano, L. R. M. (2019) · doi:10.11606/t.17.2019.tde-30052019-151114
Liu, T., Lv, Y., Huang, X., Xie, Y., Ye, Y., Chen, Y., Feng, C., Wang, Q., Zn, M., Liao, M., et al. (2025) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.70175
Morita, A., Watanabe, K., Kondo, M., Khidkhan, K., Saengtienchai, A., Somgid, C., Towiboon, P., Angkawanish, T., Langkaphin, W., Namwongprom, K., et al. (2026) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2026.110604
Opposing Roles of CYP2E1 and ALDH2 in Binge Alcohol-Mediated Cerebellar Damage
Ruiter-Lopez, L., Rungratanawanich, W., & Song, B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156825
- Authors
- Song, B.-J., Abdelmegeed, M. A., Yoo, S.-H., Kim, B.-J., Jo, S. A., Jo, I., & Moon, K.-H.
- Affiliations
- National Institutes of Health (US)
- Dankook University (KR)
- Ewha Womans University (KR)
- Corresponding author
- Song, Byoung-Joon
- Venue
- Journal of Proteomics
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 74
- Issue
- 12
- Pages
- 2691-2702
- ISSN
- 1874-3919 (ISSN-L)
- PMC
- PMC3177986
- OpenAlex
- W1995928536
- Cited by
- 73
- References
- 137
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 7 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 11 · 2013: 7 · 2012: 4
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Proteomics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism
- Center for Biological Modulators in South Korea
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- ALDH2, post-translational modification, mitochondrial enzymes, acetaldehyde metabolism, lipid hydroperoxides, cancer risk, myocardial infarction, alcoholic liver disease
- MeSH terms
- Aldehyde Dehydrogenase, Mitochondrial, Acetaldehyde, Aldehyde Dehydrogenase, Animals, Genes, Dominant, Humans, Lipid Peroxides, Liver Diseases, Alcoholic, Mutation, Myocardial Infarction, Neoplasms, Protein Processing, Post-Translational, Risk Factors, Enzyme Activators, Mitochondrial Proteins, Asian People
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