An early event in the induction of apoptosis is cytochrome c (Cyt c) release from mitochondria. We investigated the involvement of mitochonrial permeability transition (MPT) and mitochondrial swelling in Cyt c release from mitochondria treated with alloxan and/or calcium (Ca<sup>2+</sup>). When mitochondria were treated with a high concentration of Ca<sup>2+</sup>. alone or Ca<sup>2+</sup>. with alloxan (alloxan-Ca<sup>2+</sup>), the MPT was accompanied by mitochondrial swelling and the release of Cyt c. Cyclosporin A prevented the induction of MPT but only slightly decreased the release of Cyt c. High molecular weight polyethylene glycol almost completely inhibited MPT-dependent osmotic mitochondrial swelling and Cyt c release. However, MPT-independent mitochondrial swelling and Cyt c release induced by exogenous K<sup>+</sup>. were inhibited by the high molecular weight polyethylene glycol. Ruthenium red strongly decreased the amount of Cyt c released. These results suggest that mitochondrial swelling but not MPT is necessary for Cyt c release induced by Ca<sup>2+</sup> alone or alloxan and Ca<sup>2+</sup>.
KeywordsMitochondrial SwellingCytochrome C ReleaseCalciumAlloxanMitochondrial Permeability Transition
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