Synergistic effect of Ca2+ and peroxidized cardiolipin in the induction of permeability transition and cytochrome c release in rat heart mitochondria

Department of Biochemistry and Molecular Biology, University of Bari, Italy.
The Italian journal of biochemistry 01/2008; 56(4):307-9.
Source: PubMed


The effect of peroxidized cardiolipin on the mitochondrial pore transition (MPT) induction and cytochrome c release in rat heart mitochondria was studied. Treatment of mitochondria with cardiolipin hydroperoxide (CLOOH) promoted matrix swelling and release of cytochrome c. Both these processes were inhibited by cyclosporine A and bongkrekic acid, indicating that peroxidized cardiolipin behaves as an inducer of MPT. Ca2+ accumulation was required for this effect. ANT (ADP/ATP carrier) is involved in the CLOOH-dependent MPT induction as suggested by the modulation by ligands and inhibitors of ANT. These results indicate that CLOOH lowers the threshold of Ca2+ for MPT induction. This synergistic effect of Ca2+ and CLOOH on MPT induction and cytochrome c release in mitochondria might have important implications in the apoptotic process as well as in several pathophysiological situations.

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    • "All of this results in inhibition of mitochondrial respiration and sets the stage for apoptosis (Gonzalvez and Gottlieb, 2007; Schug and Gottlieb, 2009). Oxidized cardiolipin synergizes with Ca 2+ to induce opening of the mitochondrial permeability transition (MPT) pore (Petrosillo et al., 2007). The identity of the MPT pore remains "
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