Mitochondrial electron transport can become a significant source of oxidative injury in cardiomyocytes

Terry L. Vanden Hoek, Zuohui Shao, Changqing Li, Paul T. Schumacker, Lance B. Becker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


Ischemia/reperfusion causes oxidant injury in isolated cardiomyocytes without neutrophils or xanthine oxidase. Since these cells contain mitochondria, we hypothesized that the mitochondrial electron transport chain (ETC) causes this injury. To test this, we altered two conditions known to change within the mitochondria during ischemia/reperfusion - the extent of ETC redox-reduction and oxygen levels - and measured the resulting oxidant generation and injury. Specifically, we exposed cardiomyocytes for 1 h to the mitochondrial ETC inhibitors cyanide, antimycin, and rotenone and measured oxidant generation, using the intracellular fluorescent probe 2',7'-dichlorofluorescin (DCFH, sensitive to H2O2 and hydroxyl radicals). Inhibitors causing more extensive redox-reduction of the ETC (cyanide or antimycin) generated more oxidants than did partial ETC reduction with the inhibitor rotenone (10-fold v five-fold increases in DCFH oxidation). In addition, the DCFH oxidation caused by cyanide could be completely attenuated by the antioxidants 2-mercaptopropionylglycine (MPG) and 1,10 phenanthroline (PHEN). Finally, we tested the relevance of this oxidant generation on cell survival and contraction, with and without antioxidant interventions. Cell viability and contraction after 3-h recovery from cyanide exposure was significantly improved by either the addition of antioxidants, or by the 'antioxidant' strategy of lowering O2 levels (i.e. from 150 to 3 τ) during the cyanide exposure (13.8% death with hypoxic cyanide v 48.6% cell death with normoxic cyanide). Collectively, these findings demonstrate that mitochondrial ETC carriers can cause significant oxidant injury, greatest when fully redox-reduced and exposed to oxygen, conditions known to occur in the transition from ischemia to reperfusion.

Original languageEnglish (US)
Pages (from-to)2441-2450
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Issue number9
StatePublished - Sep 1997


  • Antimycin
  • Cardiomyocytes
  • Cell survival
  • Chemical hypoxia
  • Contractile function
  • Cyanide
  • Electron transport inhibition
  • Reactive oxygen species
  • Rotenone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology


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