Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2- nonenal

Kenneth M. Humphries, Young Yoo, Luke I. Szweda

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

During the progression of certain degenerative conditions, including myocardial ischemia-reperfusion injury, mitochondria are a source of increased free-radical generation and exhibit declines in respiratory function(s). It has therefore been suggested that oxidative damage to mitochondrial components plays a critical role in the pathology of these processes. Polyunsaturated fatty acids of membrane lipids are prime molecular targets of free-radical damage. A major product of lipid peroxidation, 4- hydroxy-2-nonenal (HNE), is highly cytotoxic and can readily react with and damage protein. In this study, the effects of HNE on intact cardiac mitochondria were investigated to gain insight into potential mechanisms by which free radicals mediate mitochondrial dysfunction. Exposure of mitochondria to micromolar concentrations of HNE caused rapid declines in NADH-linked but not succinate-linked state 3 and uncoupled respiration. The activity of complex I was unaffected by HNE under the conditions of our experiments. Loss of respiratory activity reflected the inability of HNE- treated mitochondria to meet NADH demand during maximum rates of O2 consumption. HNE exerted its effects on intact mitochondria by inactivating α-ketoglutarate dehydrogenase. These results therefore identify a potentially important mechanism by which free radicals bring about declines in mitochondrial respiration.

Original languageEnglish (US)
Pages (from-to)552-557
Number of pages6
JournalBiochemistry
Volume37
Issue number2
DOIs
StatePublished - Jan 13 1998

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Mitochondria
NAD
Respiration
Free Radicals
Myocardial Reperfusion Injury
Succinic Acid
Pathology
Membrane Lipids
Reperfusion Injury
Unsaturated Fatty Acids
Lipid Peroxidation
Myocardial Ischemia
Oxidoreductases
2-nonenal
4-hydroxy-2-nonenal
Lipids
Proteins
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2- nonenal. / Humphries, Kenneth M.; Yoo, Young; Szweda, Luke I.

In: Biochemistry, Vol. 37, No. 2, 13.01.1998, p. 552-557.

Research output: Contribution to journalArticle

Humphries, Kenneth M. ; Yoo, Young ; Szweda, Luke I. / Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2- nonenal. In: Biochemistry. 1998 ; Vol. 37, No. 2. pp. 552-557.
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