Synergistic effect of Ca2+ and peroxidized cardiolipin in the induction of permeability transition and cytochrome c release in rat heart mitochondria.
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.
Petrosillo
Giuseppe
G
Department of Biochemistry and Molecular Biology, University of Bari, Italy. g.petrosillo@biologia.uniba.it
Casanova
Giacoma
G
Matera
Mariagiuseppa
M
Ruggiero
Francesca Maria
FM
Paradies
Giuseppe
G
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002308:Cardiolipins / Q000737:chemistry / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008054:Lipid Peroxides / Q000737:chemistry; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats
D002308:Cardiolipins; D008054:Lipid Peroxides; D045304:Cytochromes c; D002118:Calcium