The role of mitochondria in the salvage and the injury of the ischemic myocardium.
The relationships between mitochondrial derangements and cell necrosis are exemplified by the changes in the function and metabolism of mitochondria that occur in the ischemic heart. From a mitochondrial point of view, the evolution of ischemic damage can be divided into three phases. The first is associated with the onset of ischemia, and changes mitochondria from ATP producers into powerful ATP utilizers. During this phase, the inverse operation of F0F1 ATPase maintains the mitochondrial membrane potential by using the ATP made available by glycolysis. The second phase can be identified from the functional and structural alterations of mitochondria caused by prolongation of ischemia, such as decreased utilization of NAD-linked substrates, release of cytochrome c and involvement of mitochondrial channels. These events indicate that the relationship between ischemic damage and mitochondria is not limited to the failure in ATP production. Finally, the third phase links mitochondria to the destiny of the myocytes upon post-ischemic reperfusion. Indeed, depending on the duration and the severity of ischemia, not only is mitochondrial function necessary for cell recovery, but it can also exacerbate cell injury.
Di Lisa
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Dipartimento di Chimica Biologica, Università di Padova, Via G. Colombo 3, 35121 Padua, Italy. dilisa@civ.bio.unipd.it
Menabò
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Canton
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Petronilli
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V
D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000502:physiology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D010101:Oxygen Consumption; D006180:Proton-Translocating ATPases / Q000378:metabolism
D003574:Cytochrome c Group; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D006180:Proton-Translocating ATPases; D002118:Calcium