Mitochondria and ischemia-reperfusion injury of the heart: fixing a hole.
Ischemia and post-ischemic reperfusion cause a wide array of functional and structural alterations of mitochondria. Although mitochondrial impairment is recognized as pivotal in determining loss of viability, the causal relationships among the various processes involved is ill defined. Nevertheless, a wide consensus exists in attributing a crucial role to opening of the mitochondrial permeability transition pore (PTP). Strong support for this concept has recently been provided by the reduced infarct size observed in mice lacking cyclophilin D. This protein located within the mitochondrial matrix favours PTP opening by increasing its sensitivity to Ca2+ in a process that is antagonized by cyclosporin A. Genetic approaches have also been used to demonstrate that adenine nucleotide translocase is not an essential component of the PTP. Here, we discuss our current understanding of the structure and function of PTP in the context of heart injury caused by ischemia and reperfusion.
Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.dilisa@civ.bio.unipd.it
Fabio
F
Di Lisa
Paolo
P
Bernardi
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C000631446:PPIF protein, mouse; D017382:Reactive Oxygen Species; D021983:Cyclophilins; D002118:Calcium