TY - JOUR
T1 - Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications
AU - Song, Byoung Joon
AU - Abdelmegeed, Mohamed A.
AU - Yoo, Seong Ho
AU - Kim, Bong Jo
AU - Jo, Sangmee A.
AU - Jo, Inho
AU - Moon, Kwan Hoon
N1 - Funding Information:
This research was supported by the Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism . Part of this research was also supported by a grant for the Chronic Liver Disease Project (to B.J. Song) from the Center for Biological Modulators in South Korea . We are grateful to Drs. Timothy D. Veenstra, Brian L. Hood, Thomas P. Conrads, Li-Rong Yu, and Xiaoying Ye at the Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick Inc, Frederick, Maryland for the mass-spectral analysis to determine the identities of the oxidatively-modified proteins in our experimental models. We also thank Dr. Klaus Gawrisch for his support. The authors do not have any conflict of interest.
PY - 2011/11/18
Y1 - 2011/11/18
N2 - 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.
AB - 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.
KW - Aldehyde dehydrogenases
KW - Cellular defense
KW - Disease states
KW - Drug toxicity
KW - Post-translational modifications
KW - Translational research
UR - http://www.scopus.com/inward/record.url?scp=81055158018&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2011.05.013
DO - 10.1016/j.jprot.2011.05.013
M3 - Review article
C2 - 21609791
AN - SCOPUS:81055158018
SN - 1874-3919
VL - 74
SP - 2691
EP - 2702
JO - Journal of Proteomics
JF - Journal of Proteomics
IS - 12
ER -