Protection by thiols of the mitochondrial complexes from 4-hydroxy-2-nonenal

Lioubov G. Korotchkina, Hsin Sheng Yang, Oren Tirosh, Lester Packer, Mulchand S. Patel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


In the present study, the effects of 4-hydroxy-2-nonenal (HNE) on highly purified pyruvate dehydrogenase complex (PDC) and its catalytic components in vitro and on PDC, α-ketoglutarate dehydrogenase complex (KGDC), and the branched-chain α-keto acid dehydrogenase complex (BCKDC) activities in cultured human HepG2 cells were investigated. Among the PDC components, the activity of the dihydrolipoamide acetyltransferase-E3-binding protein subcomplex (E2-E3BP) only was decreased by HNE. Dihydrolipoamide dehydrogenase (E3) protected the E2-E3BP subcomplex from HNE inactivation in the absence of the substrates. In the presence of E3 and NADH, when lipoyl groups were reduced, higher inactivation of the E2-E3BP subcomplex by HNE was observed. Purified PDC was protected from HNE-induced inactivation by several thiol compounds including lipoic acid plus [LA-plus; 2-(N,N-dimethylamine)ethylamidolipoate HCl]. Treatment of cultured HepG2 cells with HNE resulted in a significant reduction of PDC and KGDC activities, whereas BCKDC activity decreased to a lesser extent. Lipoyl compounds afforded protection from HNE-induced inhibition of PDC. This protection was higher in the presence of cysteine and reduced glutathione. Cysteine was able to restore PDC activity to some extent after HNE treatment. These findings show that thiols, including lipoic acid, provide protection against HNE-induced inactivation of lipoyl-containing complexes in the mitochondria.

Original languageAmerican English
Pages (from-to)992-999
Number of pages8
JournalFree Radical Biology and Medicine
Issue number9
StatePublished - 1 May 2001
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported in part by NIH grants DK20478 (MSP), DK42885 (MSP), and DK50430 (LP).


  • 4-Hydroxy-2-nonenal
  • Branched-chain α-keto acid dehydrogenase complex
  • Cysteine
  • Free radicals
  • Glutathione
  • HepG2 cells
  • Lipoic acid plus
  • Lipoyl compounds
  • Pyruvate dehydrogenase complex
  • α-Ketoglutarate dehydrogenase complex


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