Mitochondrial contribution in the progression of cardiac ischemic injury.
The multifaceted relationship between mitochondria and the rest of the cell is reviewed in the context of myocardial ischemia. Paradoxically, mitochondria can exacerbate the ischemic damage, especially at the onset of reperfusion. Indeed, the recovery of oxidative phosphorylation in the presence of an excessive energy demand is likely to represent a crucial factor in the ensuing irreversible damage of cardiomyocytes. A major role in the progression towards cell death might be attributed to the opening of the permeability transition pore, which besides abolishing mitochondrial ATP production might amplify the damage by causing NAD+ release. This damaging role is balanced by the contribution of mitochondria in self-defense mechanisms operating in the ischemic cardiomyocytes. The mitochondrial ATP-sensitive K+ channel and a slight increase in the production of reactive oxygen species appear to mediate the attempt of the heart to maintain its viability under conditions of acute and chronic ischemia. The significance of the various processes is discussed along with the critical evaluation of both the difficulties in studying mitochondria in situ and the possible sources of errors or misinterpretations.
Di Lisa
F
F
Dipartimento di Chimica Biologica, Universitá di Padova, Italy. dilisa@civ.bio.unipd.it
D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010539:Permeability; D015424:Reperfusion
D009243:NAD; D010100:Oxygen