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

Research output: Contribution to journalReview articlepeer-review

53 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 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.

Original languageEnglish
Pages (from-to)2691-2702
Number of pages12
JournalJournal of Proteomics
Volume74
Issue number12
DOIs
StatePublished - 18 Nov 2011

Keywords

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

Fingerprint

Dive into the research topics of 'Post-translational modifications of mitochondrial aldehyde dehydrogenase and biomedical implications'. Together they form a unique fingerprint.

Cite this