A permeability transition in liver mitochondria and liposomes induced by α,ω-dioic acids and Ca2+
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The article examines the molecular mechanism of the Ca2+-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 Ca2+-loaded liver mitochondria was shown to induce a high-amplitude swelling of the organelles, a drop of membrane potential and the release of Ca2+ 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 Ca2+ to HDA-containing liposomes did not change the phase state of liposomal membranes—in contrast to what was observed when Ca2+ was added to PA-containing vesicles. It was suggested that HDA/Ca2+- and PA/Ca2+-induced permeability transition occurs by different mechanisms. Using the method of dynamic light scattering, we further revealed that the addition of Ca2+ 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/Ca2+-induced permeability transition of the mitochondrial membrane is discussed.
KeywordsLiver mitochondria α,ω-Dioic acids Ca2+ Liposome Lipid pore Membrane fusion
Large unilamellar vesicle
We are grateful to Dr. Alexey Agafonov for fruitful discussions. This study was supported by the Ministry of Education and Science of the Russian Federation (Project No. 1365) by the Government of RF (Project No. 14.Z50.31.0028) and by grants from the Russian Foundation for Basic Research (14-04-00688-a, 12-04-00430-a; 14-34-50380).
- Agafonov AV, Gritsenko EN, Shlyapnikova EN, Kharakoz DP, Belosludtseva NV, Lezhnev EI, Saris Nils-Erik L, Mironova GD (2007) Ca2+-induced phase separation in the membrane of palmitate-containing liposomes and its possible relation to membrane permeabilization. J Membr Biol 215:57–68PubMedCrossRefGoogle Scholar
- Dubinin MV, Vedernikov AA, Adakeeva SI, Khoroshavina EI, Samartsev VN (2014) Physiological modulators of cyclosporin A-insensitive nonspecific permeability of the inner membrane of liver mitochondria induced by calcium ions and α, ω-hexadecanedioic acid. Biochem (Mosc) Suppl Ser A Membr Cell Biol 8:30–36CrossRefGoogle Scholar
- Kamo N, Muratsugu M, Hongoh R, Kobatake Y (1979) Membrane potential of mitochondria measured with an electrode sensitive to tetraphenylphosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state. J Membr Biol 49:105–121PubMedCrossRefGoogle Scholar
- Kates M (1972) Techniques of Lipidology. Isolation, analysis and identification of lipids. Elsevier, New YorkGoogle Scholar
- Kharakoz DP, Panchelyuga MS, Tiktopulo EI, Shlyapnikova EA (2007) Critical temperatures and a critical chain length in saturated diacylphosphatidylcholines: calorimetric, ultrasonic and Monte Carlo simulation study of chain-melting/ordering in aqueous lipid dispersions. Chem Phys Lipids 150:217–228PubMedCrossRefGoogle Scholar
- Markova OV, Bondarenko DI, Samartsev VN (1999) The anion-carrier mediated uncoupling effect of dicarboxylic fatty acids in liver mitochondria depends on the position of the second carboxyl group. Biochemistry (Moscow) 64:565–570Google Scholar
- Mironova GD, Gateau-Roesch O, Levrat C, Gritsenko E, Pavlov E, Lazareva AV, Limarenko E, Rey P, Louisot P, Saris N-EL (2001) Palmitic and stearic acids bind Ca2+ with high affinity and form nonspecific channels in black-lipid membranes. Possible relation to Ca2+-activated mitochondrial pores. J Bioenerg Biomembr 33:319–331PubMedCrossRefGoogle Scholar
- Mironova GD, Gritsenko E, Gateau-Roesch O, Levrat C, Agafonov A, Belosludtsev K, Prigent A, Muntean D, Dubois M, Ovize M (2004) Formation of palmitic acid/Ca2+ complexes in the mitochondrial membrane: a possible role in the cyclosporin-insensitive permeability transition. J Bioenerg Biomembr 36:171–178PubMedCrossRefGoogle Scholar