Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells

Attila Bacsi, Mitchell Woodberry, William Widger, John Papaconstantinou, Sankar Mitra, Johnny W. Peterson, Istvan Boldogh

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

3-Nitropropionic acid (3-NPA), an inhibitor of succinate dehydrogenase (SDH) at complex II of the mitochondrial electron transport chain induces cellular energy deficit and oxidative stress-related neurotoxicity. In the present study, we identified the site of reactive oxygen species production in mitochondria. 3-NPA increased O2{radical dot} - generation in mitochondria respiring on the complex I substrates pyruvate + malate, an effect fully inhibited by rotenone. Antimycin A increased O2{radical dot} - production in the presence of complex I and/or II substrates. Addition of 3-NPA markedly increased antimycin A-induced O2{radical dot} - production by mitochondria incubated with complex I substrates, but 3-NPA inhibited O2{radical dot} - formation driven with the complex II substrate succinate. At 0.6 μM, myxothiazol inhibits complex III, but only partially decreases complex I activity, and allowed 3-NPA-induced O2{radical dot} - formation; however, at 40 μM myxothiazol (which completely inhibits both complexes I and III) eliminated O2{radical dot} - production from mitochondria respiring via complex I substrates. These results indicate that in the presence of 3-NPA, mitochondria generate O2{radical dot} - from a site between the ubiquinol pool and the 3-NPA block in the respiratory complex II.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalMitochondrion
Volume6
Issue number5
DOIs
StatePublished - Oct 2006

Keywords

  • 3-NPA
  • Mitochondrial respiratory complexes
  • Superoxide anion

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology

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