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

Korge, Paavo, Henry M. Honda, and James N. Weiss. Regulation of the mitochondrial permeability transition by matrix Ca and voltage during anoxia/reoxygenation. Am J Physiol Cell Physiol 280: C517–C526, 2001.—We studied the interplay between matrix Ca concentration ([Ca]) and mitochondrial membrane potential (Dc) in regulation of the mitochondrial permeability transition (MPT) during anoxia and reoxygenation. Without Ca loading, anoxia caused near-synchronous Dc dissipation, mitochondrial Ca efflux, and matrix volume shrinkage when a critically low PO2 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] was increased to promote significant Ca uptake during anoxia, depending on the Ca load size and ability to maintain Dc. However, when [Ca] was increased after complete Dc dissipation, MPT did not occur until reoxygenation, at which time reactivation of electron transport led to partial Dc regeneration. In the setting of elevated extramitochondrial Ca, this enhanced matrix Ca uptake while promoting MPT because of less than full recovery of Dc. The interplay between Dc and matrix [Ca] in accelerating or inhibiting MPT during anoxia/reoxygenation has implications for preventing reoxygenation injury associated with MPT.