Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications

Byoung Joon Song; Mohamed A. Abdelmegeed; Seong Ho Yoo; Bong Jo Kim; Sangmee A. Jo; Inho Jo; Kwan Hoon Moon

doi:10.1016/j.jprot.2011.05.013

Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications

Byoung Joon Song, Mohamed A. Abdelmegeed, Seong Ho Yoo, Bong Jo Kim, Sangmee A. Jo, Inho Jo, Kwan Hoon Moon

Department of Molecular Medicine

Research output: Contribution to journal › Review article › peer-review

60 Scopus citations

Abstract

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 K_m 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.

Original language	English
Pages (from-to)	2691-2702
Number of pages	12
Journal	Journal of Proteomics
Volume	74
Issue number	12
DOIs	https://doi.org/10.1016/j.jprot.2011.05.013
State	Published - 18 Nov 2011

Bibliographical note

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.

Keywords

Aldehyde dehydrogenases
Cellular defense
Disease states
Drug toxicity
Post-translational modifications
Translational research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jprot.2011.05.013

Cite this

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title = "Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications",

abstract = "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.",

keywords = "Aldehyde dehydrogenases, Cellular defense, Disease states, Drug toxicity, Post-translational modifications, Translational research",

author = "Song, {Byoung Joon} and Abdelmegeed, {Mohamed A.} and Yoo, {Seong Ho} and Kim, {Bong Jo} and Jo, {Sangmee A.} and Inho Jo and Moon, {Kwan Hoon}",

note = "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.",

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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.

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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.

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KW - Cellular defense

KW - Disease states

KW - Drug toxicity

KW - Post-translational modifications

KW - Translational research

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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 -

Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications

Abstract

Bibliographical note

Keywords

UN SDGs

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