4-hydroxy-2-nonenal mediated declines in mitochondrial respiration

K. M. Humphries, L. I. Szweda

Research output: Contribution to journalArticle

Abstract

Mitochondria are a source of free radicals. 1 he production ol which inciears with age and during tin1 progression certain diseases. It is therefore likely thai free radical damage to mitochondria! components plays an important role in lhe.se degenerative proroges. Kree radicals readily react with pnlyun.-aturated fatty acids, producing toxic aldehyde species, -t-Hydroxy-2-nonenal (HNKi. a major product of lipid peroxidation, is believed (o be the most reactive ni the known products under physiological conditions. HNF, has been >iiown to be reactive with proteins and tan inhibit enzyme function. Information on the effects of HNF on mitochondria would therefore provide insight info potential mechanisms of mitochondrial dysfunction associated with oxidaiive stress. Rat heart mitochondria incubated with HNK exhibit declines in N ADH linked State :i respiration. Inhibition is first order with respect to time and is dependent upon the concentration of HNK (//M range) and mitochondria. The degree of inactiva.tion by H\K was identical when O2 consumption wa.s assessed in the presence of uncouplcrs. In contrast. HNE had no effect on succinate-linkcd {N'ADH-independent ) respiration. These observations suggest that either complex I of the electron transport chain or the production of NADH is inhibited by HNK. Studies are underway to determine which of these processes are affected by HNK and to identify specific mitochondrial proteins modified by II.XK. The results oft hese studies indicate potential mechanisms by which free radicals and. in particular, lipid peroxidatkm mediate mi ten hoi id rial dvsfunrtion.

Original languageEnglish (US)
Pages (from-to)A1261
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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