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Blockade of electron transport during ischemia protects cardiac mitochondria

Edward J Lesnefsky1, Qun Chen, Shadi Moghaddas

  • 1Department of Medicine, Division of Cardiology, School of Dentistry, Case Western Reserve University, Cleveland, Ohio 44106, USA. EXL9@po.cwru.edu

The Journal of Biological Chemistry
|September 7, 2004
PubMed

Insights

Inhibiting mitochondrial complex I during ischemia preserves heart mitochondria by reducing reactive oxygen species. This protects cardiolipin and cytochrome c, lessening damage during reperfusion.

Area of Science:

  • Cardiology
  • Mitochondrial Biology
  • Biochemistry

Background:

  • Subsarcolemmal mitochondria are vulnerable to damage during myocardial ischemia.
  • Ischemia leads to decreased cardiolipin and cytochrome c, impairing cytochrome oxidase function.
  • Mitochondrial reactive oxygen species (ROS) production in the electron transport chain contributes to ischemic injury.

Purpose of the Study:

  • To investigate if inhibiting complex I of the electron transport chain protects mitochondria during ischemia.
  • To determine the role of ROS produced by the electron transport chain in ischemic mitochondrial damage.

Main Methods:

  • Isolated, perfused rabbit hearts were pretreated with rotenone, a complex I inhibitor, before inducing ischemia.
  • Cardiolipin and cytochrome c content were measured after ischemia.
  • The rate of oxidation through cytochrome oxidase was assessed.
  • ROS production in isolated subsarcolemmal mitochondria was measured during substrate oxidation.

Main Results:

  • Rotenone pretreatment preserved cardiolipin and cytochrome c content after ischemia.
  • The rate of oxidation through cytochrome oxidase was improved in rotenone-treated hearts.
  • Rotenone treatment reduced ROS production during complex I substrate oxidation in isolated mitochondria.

Conclusions:

  • Inhibiting the mitochondrial electron transport chain during ischemia mitigates mitochondrial damage.
  • Limiting electron flow preserves mitochondrial function and reduces ROS production.
  • The mitochondrial electron transport chain is a significant contributor to ischemic mitochondrial damage, exacerbating myocyte injury upon reperfusion.

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