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Cardioprotection by modulation of mitochondrial respiration during ischemia-reperfusion: role of apoptosis-inducing

Aijun Xu1, Karol Szczepanek, Ying Hu

  • 1Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298, USA.

Biochemical and Biophysical Research Communications
|May 21, 2013
PubMed

Insights

Transient, reversible blockade of electron transport (BET) protects the heart by preventing the release of apoptosis-inducing factor (AIF) from mitochondria during ischemia-reperfusion injury. This mechanism reduces cardiac damage, even in models with reduced AIF levels.

Area of Science:

  • Cardiovascular Science
  • Mitochondrial Biology
  • Cell Death Mechanisms

Background:

  • Mitochondrial dysfunction and apoptosis-inducing factor (AIF) release contribute to cardiac injury during ischemia-reperfusion.
  • Transient, reversible blockade of electron transport (BET) is a known cardioprotective strategy.

Purpose of the Study:

  • To investigate if BET prevents AIF release from mitochondria as a mechanism of cardioprotection.
  • To determine if BET-mediated protection is dependent on mitochondrial AIF levels.

Main Methods:

  • Utilized amobarbital, a mitochondrial complex I inhibitor, to induce BET in buffer-perfused rat hearts.
  • Assessed AIF release, cleaved PARP-1 formation, and cardiac injury.
  • Employed Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, to test BET's efficacy in AIF-deficient hearts.

Main Results:

  • BET significantly attenuated the release of AIF from mitochondria into the cytosol during ischemia.
  • BET decreased the formation of cleaved and activated PARP-1, indicating reduced apoptosis.
  • BET provided significant cardioprotection in Hq mouse hearts, reducing ischemia-reperfusion injury and improving mitochondrial function, despite AIF deficiency.

Conclusions:

  • BET-mediated cardioprotection involves the prevention of mitochondrial AIF loss during ischemia-reperfusion.
  • While AIF preservation contributes to BET's protective effects, the mechanism is not solely dependent on AIF-driven pathways.
  • BET offers protection against cardiac injury irrespective of normal or deficient mitochondrial AIF content.

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