Cardiolipin and apoptosis

McMillin, Jeanie B.; Dowhan, William

doi:10.1016/s1388-1981(02)00329-3

Cited by 242 publications

(202 citation statements)

References 81 publications

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“…Cardiolipin is a significant player in the apoptotic cell death program [27] and one of the major factor in the t-Bid-induced destabilization of mitochondrial bioenergetics [28]. Cardiolipin is believed to significantly contribute to the outer membrane permeabilization and cytochrome c release during apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Interaction of peroxidized cardiolipin with rat‐heart mitochondrial membranes: Induction of permeability transition and cytochrome c release

et al. 2006

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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, DW 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.

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Section: Discussionmentioning

confidence: 99%

Interaction of peroxidized cardiolipin with rat‐heart mitochondrial membranes: Induction of permeability transition and cytochrome c release

et al. 2006

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“…Clinical studies have associated sterility with oxidative stress-mediated DNA damage in spermatozoa [23][24][25]. As was previously mentioned, mitochondrial CL would dissociate from the Cyt C-CL complex upon oxidation, and subsequently trigger a cascade of apoptotic events [7][8][9]. Since lipid peroxidation usually occurs at the unsaturated bonds of fatty acids, elimination of unsaturated fatty acids in testicular CL could be regarded as the result of an evolutionary-derived protective mechanism to increase the fertility of spermatozoa by reducing their chance of undergoing lipid per- oxidation through oxidative stress in its highly specialized functional environment [23][24][25].…”

Section: Distribution Of Major CL Species In Rat Organsmentioning

confidence: 97%

“…In addition, CL is also the critical component for the assembly of mitochondria supercomplex consisting of Complexes III and IV [7]. Several earlier studies of oxidative stress-mediated apoptosis demonstrated that mitochondria directly or indirectly subjected to oxidative stress disrupted the homeostasis between CL and Cyt C [7][8][9] and caused the dissociation of Cyt C-CL complexes. Upon dissociation, Cyt C is released from the inner mitochondrial membrane and eventually escapes to the cytoplasm, where it triggers a cascade of events leading to programmed cell death [7].…”

mentioning

confidence: 99%

Direct MALDI-MS analysis of cardiolipin from rat organs sections

Wang

Jackson

Woods

2007

J. Am. Soc. Mass Spectrom.

109

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Cardiolipins (CL) are mitochondria specific lipids. They play a critical role in ATP synthesis mediated by oxidative phosphorylation. Abnormal CL distribution is associated with several disease states. MALDI-MS and MALDI-MS/MS were used to demonstrate in situ analysis and characterization of CL from tissue sections of organs containing high concentrations of mitochondria. Once the experimental parameters were established, a survey of CL distribution in heart, liver, kidney, leg muscle, and testis was undertaken. The major CL specie in the heart muscle, leg muscle, liver, and kidney is the (18:2) 4 CL, while liver and kidney also contain a minor specie, (18:2) 3 /(18:1) CL. The major CL specie in testis is the (16:0) 4 CL. The CL species distribution in various organs appeared to be in agreement with prior reports. Overall, proper matrix selection, tissue section handling, instrument tuning, and the inclusion of cesium ion in matrix ensured successful in situ MALDI-MS and MALDI-MS/MS analysis of CL. Upon modification and standardization, this method could be streamlined for rapid pathological diagnosis with short turnaround time in clinical settings. (J Am Soc Mass Spectrom 2007, 18, 567-577)

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“…CL has important roles in certain pathologies, such as heart ischemia and Barth's syndrome, and factors such as diet and aging can change CL levels (McMillin and Dowhan, 2002). CL contains four unsaturated fatty acids per molecule and thus is easily attacked by singlet oxygen as well as by other oxidizing agents.…”

Section: Introductionmentioning

confidence: 99%

Targeting of mitochondria by 10-N-alkyl acridine orange analogues: Role of alkyl chain length in determining cellular uptake and localization

et al. 2008

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Abstract10-N-nonyl acridine orange (NAO) is used as a mitochondrial probe because of its high affinity for cardiolipin (CL). Targeting of NAO may also depend on mitochondrial membrane potential. As the nonyl group has been considered essential for targeting, a systematic study of alkyl chain length was undertaken; three analogues (10-methyl-, 10-hexyl-, and 10-hexadecyl-acridine orange) were synthesized and their properties studied in phospholipid monolayers and breast cancer cells. The shortest and longest alkyl chains reduced targeting, whereas the hexyl group was superior to the nonyl group, allowing very clear and specific targeting to mitochondria at concentrations of 20-100 nM, where no evidence of toxicity was apparent. Additional studies in wild-type and cardiolipindeficient yeast cells suggested that cellular binding was not absolutely dependent upon cardiolipin.

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Cardiolipin and apoptosis

Cited by 242 publications

References 81 publications

Interaction of peroxidized cardiolipin with rat‐heart mitochondrial membranes: Induction of permeability transition and cytochrome c release

Interaction of peroxidized cardiolipin with rat‐heart mitochondrial membranes: Induction of permeability transition and cytochrome c release

Direct MALDI-MS analysis of cardiolipin from rat organs sections

Targeting of mitochondria by 10-N-alkyl acridine orange analogues: Role of alkyl chain length in determining cellular uptake and localization

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