Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy

A. Hamacher-Brady, N. R. Brady, S. E. Logue, M. R. Sayen, M. Jinno, L. A. Kirshenbaum, R. A. Gottlieb, Å B. Gustafsson

Research output: Contribution to journalArticlepeer-review

Abstract

Ischemia and reperfusion (I/R) injury is associated with extensive loss of cardiac myocytes. Bnip3 is a mitochondrial pro-apoptotic Bcl-2 protein which is expressed in the adult myocardium. To investigate if Bnip3 plays a role in I/R injury, we generated a TAT-fusion protein encoding the carboxyl terminal transmembrane deletion mutant of Bnip3 (TAT-Bnip3ΔTM) which has been shown to act as a dominant negative to block Bnip3-induced cell death. Perfusion with TAT-Bnip3ΔTM conferred protection against I/R injury, improved cardiac function, and protected mitochondrial integrity. Moreover, Bnip3 induced extensive fragmentation of the mitochondrial network and increased autophagy in HL-1 myocytes. 3D rendering of confocal images revealed fragmented mitochondria inside autophagosomes. Enhancement of autophagy by ATG5 protected against Bnip3-mediated cell death, whereas inhibition of autophagy by ATG5K130R enhanced cell death. These results suggest that Bnip3 contributes to I/R injury which triggers a protective stress response with upregulation of autophagy and removal of damaged mitochondria.

Original languageEnglish (US)
Pages (from-to)146-157
Number of pages12
JournalCell death and differentiation
Volume14
Issue number1
DOIs
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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