Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy

Cell Death Differ. 2007 Jan;14(1):146-57. doi: 10.1038/sj.cdd.4401936. Epub 2006 Apr 28.


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-Bnip3DeltaTM) which has been shown to act as a dominant negative to block Bnip3-induced cell death. Perfusion with TAT-Bnip3DeltaTM 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy*
  • Gene Deletion
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Mitochondria, Heart / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / isolation & purification
  • Mitochondrial Proteins / metabolism
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / physiopathology*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / isolation & purification
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • BNIP3 protein, rat
  • Membrane Proteins
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins