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

Abstract
The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia-reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia-reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in reducing cell injury during reperfusion, the protection derived from the BET is not fully dependent on AIF-driven mechanisms.
AuthorsAijun Xu, Karol Szczepanek, Ying Hu, Edward J Lesnefsky, Qun Chen
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 435 Issue 4 Pg. 627-33 (Jun 14 2013) ISSN: 1090-2104 [Electronic] United States
PMID23685150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Apoptosis Inducing Factor
  • Pdcd8 protein, mouse
Topics
  • Animals
  • Apoptosis Inducing Factor (metabolism)
  • Cell Respiration
  • Electron Transport
  • Male
  • Mice
  • Mitochondria, Heart (metabolism)
  • Rats
  • Rats, Inbred F344
  • Reperfusion Injury (physiopathology)

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