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Interaction of peroxidized cardiolipin with rat‐heart mitochondrial membranes: Induction of permeability transition and cytochrome c release
Author(s) -
Petrosillo Giuseppe,
Casanova Giacoma,
Matera Mariagiuseppa,
Ruggiero Francesca Maria,
Paradies Giuseppe
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.10.036
Subject(s) - cardiolipin , cytochrome c , mitochondrion , mitochondrial permeability transition pore , inner mitochondrial membrane , adenine nucleotide translocator , biochemistry , cytochrome , chemistry , voltage dependent anion channel , mitochondrial apoptosis induced channel , biology , microbiology and biotechnology , apoptosis , programmed cell death , membrane , phospholipid , bacterial outer membrane , enzyme , escherichia coli , gene
Cardiolipin peroxidation plays a critical role in mitochondrial cytochrome c release and subsequent apoptotic process. Mitochondrial pore transition (MPT) is considered as an important step in this process. In this work, the effect of peroxidized cardiolipin on MPT induction and cytochrome c release in rat heart mitochondria was investigated. Treatment of mitochondria with micromolar concentrations of cardiolipin hydroperoxide (CLOOH) resulted in a dose‐dependent matrix swelling, Δ Ψ collapse, release of preaccumulated Ca 2+ and release of cytochrome c . All these events were inhibited by cyclosporin A and bongkrekic acid, indicating that peroxidized cardiolipin behaves as an inducer of MPT. Ca 2+ accumulation by mitochondria was required for this effect. ANT (ADP/ATP translocator) appears to be involved in the CLOOH‐dependent MPT induction, as suggested by the modulation by ligands and inhibitors of adenine nucleotide translocator (ANT). Together, these results indicate that peroxidized cardiolipin lowers the threshold of Ca 2+ for MPT induction and cytochrome c release. This synergistic effect of Ca 2+ and peroxidized cardiolipin on MPT induction and cytochrome c release in mitochondria, might be important in regulating the initial phase of apoptosis and also may have important implications in those physiopathological situations, characterized by both Ca 2+ and peroxidized cardiolipin accumulation in mitochondria, such as aging, ischemia/reperfusion and other degenerative diseases.