Autophagy as a protective response to Bnip3-mediated apoptotic signaling in the heart.
Bnip3 is a member of the 'BH3-only' Bcl-2 subfamily which has been implicated in apoptotic,(1) necrotic(2) and autophagic cell death.(3,4) We recently reported that Bnip3 is a key mediator of mitochondrial dysfunction and cell death in the ex vivo heart following ischemia/reperfusion (I/R).(5) Moreover, we found that Bnip3 was involved in upregulation of autophagy in I/R and that Bnip3-mediated mitochondrial dysfunction correlated with upregulation of autophagy. Using a model of simulated I/R and overexpression of Bnip3 in HL-1 cardiac myocytes, we determined that Bnip3-mediated upregulation of autophagic activity constituted a protective response against Bnip3 death signaling. Here we present additional evidence that enhanced autophagic activity functions as a cytoprotective pathway to oppose ischemia/reperfusion-related apoptosis.
Hamacher-Brady
Anne
A
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Brady
Nathan R
NR
Gottlieb
Roberta A
RA
Gustafsson
Asa B
AB
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C508686:BNip3 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins