Possible Mechanism for Formation and Regulation of the Palmitate-Induced Cyclosporin A-Insensitive Mitochondrial Pore

Belosludtsev, Konstantin N.; Belosludtseva, Natalia V.; Mironova, Galina D.

doi:10.1007/s10541-005-0189-x

Cited by 24 publications

(11 citation statements)

References 18 publications

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“…As shown previously, Mg 2+ can suppress palmitate/Ca 2+ -induced permeabilization of mitochondria [9]. However, similar to other divalent cations, Mg 2+ itself is capable to trigger permeabilization of liposomes, but the efficiency of permeabilization induced by Mg 2+ was much less than by Ca 2+ , and the effect on permeabilization of 1 mM Mg 2+ was one-third that of the same concentration of Ca 2+ [11].…”

Section: Resultsmentioning

confidence: 70%

“…5). In mitochondria, millimolar Mg 2+ is required to suppress the swelling of mitochondria induced by palmitic acid and Ca 2+ [9]. …”

Section: Resultsmentioning

confidence: 99%

“…5). Earlier, we showed that Mg 2+ inhibited mitochondrial swelling as well, but the inhibitory effect of Mg 2+ on the palmitate/Ca 2+ -dependent swelling of liver mitochondria occurred in the range of 0.4–7 mM [9]. An explanation for this difference in sensitivity to Mg 2+ is that accumulation and binding of Ca 2+ to fatty acid anions takes place on in the matrix side of the mitochondria inner membrane [6], whereas access of Mg 2+ ions is restricted.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria were isolated from livers and hearts of Wistar rats (220–250 g) by differential centrifugation, as described [9]. The homogenization buffer contained 210 mM mannitol, 70 mM sucrose, 1 mM EDTA, and 10 mM Hepes/KOH buffer, pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

“…Albumin, which binds free fatty acids, and EGTA, a Ca 2+ chelator, suppress the formation of lipid pores in liver mitochondria, whereas blockers of the MPT such as CsA have no effect on opening of palmitate/Ca 2+ -induced pores in mitochondrial membranes [6, 9]. The physical–chemical properties of a lipid membrane, in particular, its phase state, depend on a number of factors: temperature, pressure, Ca 2+ , and various small molecules, including fatty acids, that interact with the bilayer-forming lipid [14].…”

Section: Introductionmentioning

confidence: 99%

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Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Belosludtsev

Belosludtseva

Агафонов

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The effect of surface-potential modulators on palmitate/Ca2+-induced formation of lipid pores was studied in liposomal and inner mitochondrial membranes. Pore formation was monitored by sulforhodamine B release from liposomes and swelling of mitochondria. ζ-potential in liposomes was determined from electrophoretic mobility. Replacement of sucrose as the osmotic agent with KCl decreased negative ζ-potential in liposomes and increased resistance of both mitochondria and liposomes to the pore inducers, palmitic acid, and Ca2+. Micromolar Mg2+ also inhibited palmitate/Ca2+-induced permeabilization of liposomes. The rate of palmitate/Ca2+-induced, cyclosporin A-insensitive swelling of mitochondria increased 22% upon increasing pH from 7.0 to 7.8. At below the critical micelle concentration, the cationic detergent cetyltrimethylammonium bromide (10 μM) and the anionic surfactant sodium dodecylsulfate (10–50 μM) made the ζ-potential less and more negative, respectively, and inhibited and stimulated opening of mitochondrial palmitate/Ca2+-induced lipid pores. Taken together, the findings indicate that surface potential regulates palmitate/Ca2+-induced lipid pore opening.

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Section: Resultsmentioning

confidence: 70%

“…5). In mitochondria, millimolar Mg 2+ is required to suppress the swelling of mitochondria induced by palmitic acid and Ca 2+ [9]. …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Belosludtsev

Belosludtseva

Агафонов

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Ca2+-Induced Phase Separation in the Membrane of Palmitate-Containing Liposomes and Its Possible Relation to Membrane Permeabilization

et al. 2007

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A Ca(2+)-induced phase separation of palmitic acid (PA) in the membrane of azolectin unilamellar liposomes has been demonstrated with the fluorescent membrane probe nonyl acridine orange (NAO). It has been shown that NAO, whose fluorescence in liposomal membranes is quenched in a concentration-dependent way, can be used to monitor changes in the volume of lipid phase. The incorporation of PA into NAO-labeled liposomes increased fluorescence corresponding to the expansion of membrane. After subsequent addition of Ca(2+), fluorescence decreased, which indicated separation of PA/Ca(2+) complexes into distinct membrane domains. The Ca(2+)-induced phase separation of PA was further studied in relation to membrane permeabilization caused by Ca(2+) in the PA-containing liposomes. A supposition was made that the mechanism of PA/Ca(2+)-induced membrane permeabilization relates to the initial stage of Ca(2+)-induced phase separation of PA and can be considered as formation of fast-tightening lipid pores due to chemotropic phase transition in the lipid bilayer.

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A permeability transition in liver mitochondria and liposomes induced by α,ω-dioic acids and Ca2+

et al. 2014

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The article examines the molecular mechanism of the Ca(2+)-dependent cyclosporin A (CsA)-insensitive permeability transition in rat liver mitochondria induced by α,ω-dioic acids. The addition of α,ω-hexadecanedioic acid (HDA) to Ca(2+)-loaded liver mitochondria was shown to induce a high-amplitude swelling of the organelles, a drop of membrane potential and the release of Ca(2+) from the matrix, the effects being insensitive to CsA. The experiments with liposomes loaded with sulforhodamine B (SRB) revealed that, like palmitic acid (PA), HDA was able to cause permeabilization of liposomal membranes. However, the kinetics of HDA- and PA-induced release of SRB from liposomes was different, and HDA was less effective than PA in the induction of SRB release. Using the method of ultrasound interferometry, we also showed that the addition of Ca(2+) to HDA-containing liposomes did not change the phase state of liposomal membranes-in contrast to what was observed when Ca(2+) was added to PA-containing vesicles. It was suggested that HDA/Ca(2+)- and PA/Ca(2+)-induced permeability transition occurs by different mechanisms. Using the method of dynamic light scattering, we further revealed that the addition of Ca(2+) to HDA-containing liposomes induced their aggregation/fusion. Apparently, these processes result in a partial release of SRB due to the formation of fusion pores. The possibility that this mechanism underlies the HDA/Ca(2+)-induced permeability transition of the mitochondrial membrane is discussed.

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Possible Mechanism for Formation and Regulation of the Palmitate-Induced Cyclosporin A-Insensitive Mitochondrial Pore

Cited by 24 publications

References 18 publications

Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Ca2+-Induced Phase Separation in the Membrane of Palmitate-Containing Liposomes and Its Possible Relation to Membrane Permeabilization

A permeability transition in liver mitochondria and liposomes induced by α,ω-dioic acids and Ca2+

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