What makes the mitochondria a killer? Can we condition them to be less destructive?
Cardioprotection, such as preconditioning and postconditioning, has been shown to result in a significant reduction in cell death. Many of the signaling pathways activated by cardioprotection have been elucidated, but there is still a lack of understanding of the mechanisms by which these signaling pathways reduce cell death. Mitochondria have been reported to be an important player in many types of apoptotic and necrotic cell death. If mitochondria play an important role in cell death, then it seems reasonable to consider that cardioprotective mechanisms might act, at least in part, by opposing mitochondrial cell death pathways. One of the major mechanisms of cell death in ischemia-reperfusion is suggested to be the opening of a large conductance pore in the inner mitochondrial membrane, known as the mitochondrial permeability transition pore. Inhibition of this mitochondrial pore appears to be one of the major mechanisms by which cardioprotection reduces cell death. Cardioprotection activates a number of signaling pathways that reduce the level of triggers (reactive oxygen species and calcium) or enhances inhibitors of the mitochondrial permeability transition pore at the start of reperfusion. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection.
Murphy
Elizabeth
E
Translational Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA. murphy1@nhlbi.nih.gov
Steenbergen
Charles
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D019157:Ischemic Preconditioning, Myocardial; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D002118:Calcium