Regulation of the mitochondrial permeability transition by matrix Ca2+ and voltage during anoxia/reoxygenation

Paavo Korge, Henry M. Honda, James N. Weiss
2001 American Journal of Physiology - Cell Physiology  
Korge, Paavo, Henry M. Honda, and James N. Weiss. Regulation of the mitochondrial permeability transition by matrix Ca 2ϩ and voltage during anoxia/reoxygenation. Am J Physiol Cell Physiol 280: C517-C526, 2001.-We studied the interplay between matrix Ca 2ϩ concentration ([Ca 2ϩ ]) and mitochondrial membrane potential (⌬) in regulation of the mitochondrial permeability transition (MPT) during anoxia and reoxygenation. Without Ca 2ϩ loading, anoxia caused near-synchronous ⌬ dissipation,
more » ... sipation, mitochondrial Ca 2ϩ efflux, and matrix volume shrinkage when a critically low PO 2 was reached, which was rapidly reversible upon reoxygenation. These changes were related to electron transport inhibition, not MPT. Cyclosporin A-sensitive MPT did occur when extramitochondrial [Ca 2ϩ ] was increased to promote significant Ca 2ϩ uptake during anoxia, depending on the Ca 2ϩ load size and ability to maintain ⌬. However, when [Ca 2ϩ ] was increased after complete ⌬ dissipation, MPT did not occur until reoxygenation, at which time reactivation of electron transport led to partial ⌬ regeneration. In the setting of elevated extramitochondrial Ca 2ϩ , this enhanced matrix Ca 2ϩ uptake while promoting MPT because of less than full recovery of ⌬. The interplay between ⌬ and matrix [Ca 2ϩ ] in accelerating or inhibiting MPT during anoxia/reoxygenation has implications for preventing reoxygenation injury associated with MPT. cardiomyocytes; mitochondrial Ca 2ϩ uptake; Ca 2ϩ efflux; permeability transition pore Address for reprint requests and other correspondence: J. N. Weiss, Div. of Cardiology, 3641 MRL Bldg.,
doi:10.1152/ajpcell.2001.280.3.c517 pmid:11171571 fatcat:ft7qgzhqhzdetmuunutycoj2va