Modulation of Mitochondrial Function by Hydrogen Peroxide

Amy C. Nulton-Persson, Luke I. Szweda

Research output: Contribution to journalArticle

304 Scopus citations

Abstract

During normal cellular metabolism, mitochondrial electron transport results in the formation of superoxide anion (O2.-) and subsequently hydrogen peroxide (H2O2). Because H 2O2 increases in concentration under certain physiologic and pathophysiologic conditions and can oxidatively modify cellular components, it is critical to understand the response of mitochondria to H2O 2. In the present study, treatment of isolated rat heart mitochondria with H2O2 resulted in a decline and subsequent recovery of state 3 NADH-linked respiration. Alterations in NADH levels induced by H2O2 closely paralleled changes in the rate of state 3 respiration. Assessment of electron transport chain complexes and Krebs cycle enzymes revealed that α-ketoglutarate dehydrogenase (KGDH), succinate dehydrogenase (SDH), and aconitase were susceptible to H 2O2 inactivation. Of particular importance, KGDH and SDH activity returned to control levels, concurrent with the recovery of state 3 respiration. Inactivation is not because of direct interaction of H 2O2 with KGDH and SDH. In addition, removal of H 2O2 alone is not sufficient for reactivation. Enzyme activity does not recover unless mitochondria remain intact. The sensitivity of KGDH and SDH to H2O2-mediated inactivation and the reversible nature of inactivation suggest a potential role for H 2O2 in the regulation of KGDH and SDH.

Original languageEnglish (US)
Pages (from-to)23357-23361
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number26
DOIs
StatePublished - Jun 29 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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