Inhibition of cytochrome c oxidase activity by 4-hydroxynonenal (HNE). Role of HNE adduct formation with the enzyme subunits

Juanjuan Chen, Steven Schenker, Teri A. Frosto, George I. Henderson

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

The role of 4-hydroxynonenal (HNE), a major lipid peroxidation product, in oxidative damage to mitochondrial cytochrome c oxidase (COX) was examined. Oxidative stress was induced in mitochondria isolated from livers of male Sprague-Dawley rats by tert-butylhydroperoxide (t-BHP). COX activity was inhibited, with a concomitant increase in endogenous HNE level in mitochondria. COX activity was also inhibited following incubation of mitochondria with 50-450 μM HNE. Blocking HNE degradation intensified COX inhibition by HNE and by t-BHP-induced oxidative stress, the latter accompanied by a simultaneous increase in endogenous HNE production. On the other hand, COX inhibition by HNE was markedly reduced by potentiating HNE degradation via enhancing conjugation of HNE with reduced glutathione (GSH). Incubation of purified COX with 10-400 μM HNE resulted in HNE adduct formation with specific subunits of COX, correlated with inhibition of the enzyme activity. These data suggest that HNE may inhibit mitochondrial COX by forming adducts with the enzyme, and that this could be one mechanism underlying mitochondrial damage caused by oxidative stress. The findings also illustrate a role for GSH in protecting mitochondria from the deleterious effects of HNE.

Original languageEnglish (US)
Pages (from-to)336-344
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1380
Issue number3
DOIs
StatePublished - May 8 1998
Externally publishedYes

Keywords

  • 4-Hydroxynonenal
  • Cytochrome c oxidase
  • Glutathione
  • Mitochondrion
  • Oxidative stress
  • Protein adduct

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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