Abstract
Mitochondria have multiple roles in the development of ischaemia/reperfusion injury. Consumption of ATP by mitochondrial ATPase during ischaemia and generation of reactive oxygen species (ROS) from complex III during ischaemia/reperfusion are detrimental to cardiomyocytes, whereas uptake of cytosolic Ca2+ into mitochondria attenuates cytosolic Ca2+ overload and thus activation of Ca2+-activated proteases such as calpain. However, the most important event in the mitochondria of cardiomyocytes subjected to ischaemia/reperfusion is opening of the mitochondrial permeability transition pore (mPTP).1 Although its molecular structure is still controversial, mPTP apparently consists of an adenine nucleotide translocator (ANT) in the inner membrane, a carrier exchanging matrix ATP with ADP in the intermembrane space,2 and a voltage-dependent anion channel (VDAC) in the outer membrane of the mitochondria.3 The mPTP is closed under physiological conditions but opens in response to cellular stresses, leading to ATP depletion, increase in inorganic phosphate levels, ROS generation, and mitochondrial Ca2+ overload. Opening of mPTP upon reperfusion following ischaemia abolishes mitochondrial membrane potential and compromises ATP generation, which is crucial for restoration of ionic homeostasis and maintenance of cell viability.4 The threshold for opening of mPTP has been shown to be elevated by ischaemic pre- … *Corresponding author. Tel: +81 11 611 2111; fax: +81 11 644 7958. E-mail address : tannom{at}sapmed.ac.jp
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