Advertisement

European Biophysics Journal

, Volume 43, Issue 10–11, pp 565–572 | Cite as

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

  • Mikhail V. DubininEmail author
  • Victor N. Samartsev
  • Maxim E. Astashev
  • Alexey S. Kazakov
  • Konstantin N. Belosludtsev
Original Paper

Abstract

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.

Keywords

Liver mitochondria α,ω-Dioic acids Ca2+ Liposome Lipid pore Membrane fusion 

Abbreviations

CsA

Cyclosporin A

HDA

α,ω-Hexadecanedioic acid

PA

Palmitic acid

TDA

α,ω-Tetradecanedioic acid

SRB

Sulforhodamine B

TPP+

Cation tetraphenylphosphonium

LUV

Large unilamellar vesicle

TX-100

Triton X-100

DPPC

1,2-Dipalmitoylphosphatidylcholine

Notes

Acknowledgments

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).

References

  1. Agafonov A, Gritsenko E, Belosludtsev K, Kovalev A, Gateau-Roesch O, Saris N-EL, Mironova GD (2003) A permeability transition in liposomes induced by the formation of Ca2+/palmitic acid complexes. Biochim Biophys Acta 1609:153–160PubMedCrossRefGoogle Scholar
  2. 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
  3. Astashev ME, Belosludtsev KN, Kharakoz DP (2014) Method for digital measurement of phase–frequency characteristics for a fixed length ultrasonic spectrometer. Acoust Phys 60:335–341CrossRefGoogle Scholar
  4. Bartlett GR (1959) Phosphorus assay in column chromatography. J Biol Chem 234:466–468PubMedGoogle Scholar
  5. Belosludtsev KN, Belosludtseva NV, Mironova GD (2005) Possible mechanism for formation and regulation of the palmitate-induced cyclosporin A-insensitive mitochondrial pore. Biochemistry (Moscow) 70:815–821CrossRefGoogle Scholar
  6. Belosludtsev K, Saris N-E, Andersson LC, Belosludtseva N, Agafonov A, Sharma A, Moshkov DA, Mironova GD (2006) On the mechanism of palmitic acid-induced apoptosis: the role of a pore induced by palmitic acid and Ca2+ in mitochondria. J Bioenerg Biomembr 38:113–120PubMedCrossRefGoogle Scholar
  7. Belosludtsev KN, Belosludtseva NV, Agafonov AV, Astashev ME, Kazakov AS, Saris N-EL, Mironova GD (2014) Ca2+-dependent permeabilization of mitochondria and liposomes by palmitic and oleic acids: a comparative study. Biochim Biophys Acta 1838:2600–2606PubMedCrossRefGoogle Scholar
  8. Chernomordik LV, Kozlov MM (2003) Protein-lipid interplay in fusion and fission of biological membranes. Annu Rev Biochem 72:175–207PubMedCrossRefGoogle Scholar
  9. Chernomordik LV, Kozlov MM (2008) Mechanics of membrane fusion. Nat Struct Mol Biol 15:675–683PubMedCrossRefPubMedCentralGoogle Scholar
  10. Di Paola M, Lorusso M (2006) Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition. Biochim Biophys Acta 1757:1330–1337PubMedCrossRefGoogle Scholar
  11. Dubinin MV, Adakeeva SI, Samartsev VN (2013) Long-chain α, ω-dioic acids as inducers of cyclosporin A-insensitive nonspecific permeability of the inner membrane of liver mitochondria loaded with calcium or strontium ions. Biochemistry (Moscow) 78:412–417CrossRefGoogle Scholar
  12. 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
  13. Ferdinandusse S, Denis S, Van Roermund C, Wanders RJ, Dacremont G (2004) Identification of the peroxisomal β-oxidation enzymes involved in the degradation of long-chain dicarboxylic acids. J Lipid Res 45:1104–1111PubMedCrossRefGoogle Scholar
  14. Jackson MB, Chapman ER (2008) The fusion pores of Ca2+-triggered exocytosis. Nat Struct Mol Biol 15:684–689PubMedCrossRefPubMedCentralGoogle Scholar
  15. 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
  16. Kates M (1972) Techniques of Lipidology. Isolation, analysis and identification of lipids. Elsevier, New YorkGoogle Scholar
  17. 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
  18. Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163PubMedCrossRefGoogle Scholar
  19. Kundu RK, Tonsgard JH, Getz GS (1991) Induction of omega-oxidation of monocarboxylic acids in rats by acetylsalicylic acid. J Clin Invest 88:1865–1872PubMedCrossRefPubMedCentralGoogle Scholar
  20. Lentz BR, Malinin V, Haque ME, Evans K (2000) Protein machines and lipid assemblies: current views of cell membrane fusion. Curr Opin Struct Biol 10:607–615PubMedCrossRefGoogle Scholar
  21. Malhi H, Guicciardi ME, Gores GL (2010) Hepatocyte death: a clear and present danger. Physiol Rev 90:1165–1194PubMedCrossRefPubMedCentralGoogle Scholar
  22. 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
  23. 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
  24. 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
  25. Nelson CJ, Otis JP, Martin SL, Carey HV (2009) Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver. Physiol Genomics 37:43–51PubMedCrossRefGoogle Scholar
  26. Orellana M, Rodrigo R, Valdes E (1998) Peroxisomal and microsomal fatty acid oxidation in liver of rats after chronic ethanol consumption. Gen Pharmacol 31:817–820PubMedCrossRefGoogle Scholar
  27. Papahadjopoulos D, Nir S, Düzgünes N (1990) Molecular mechanisms of calcium-induced membrane fusion. J Bioenerg Biomembr 22:157–179PubMedCrossRefGoogle Scholar
  28. Rasola A, Bernardi P (2011) Mitochondrial permeability transition in Ca2+-dependent apoptosis and necrosis. Cell Calcium 50:222–233PubMedCrossRefGoogle Scholar
  29. Reddy JK, Rao MS (2006) Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 290:852–858CrossRefGoogle Scholar
  30. Sanders RJ, Ofman R, Valianpou F, Kemp S, Wanders RJ (2005) Evidence for two enzymatic pathways for omega-oxidation of docosanoic acid in rat liver microsomes. J Lipid Res 46:1001–1008PubMedCrossRefGoogle Scholar
  31. Sultan A, Sokolove P (2001a) Palmitic acid opens a novel cyclosporin A-insensitive pore in the inner mitochondrial membrane. Arch Biochem Biophys 386:37–51PubMedCrossRefGoogle Scholar
  32. Sultan A, Sokolove P (2001b) Free fatty acid effects on mitochondrial permeability: an overview. Arch Biochem Biophys 386:52–61PubMedCrossRefGoogle Scholar
  33. Tonsgard JH (1986) Serum dicarboxylic acids in Reye syndrome. J Pediatr 109:440–445PubMedCrossRefGoogle Scholar
  34. Wanders RJ, Komen J, Kemp S (2011) Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans. FEBS J 278:182–194PubMedCrossRefGoogle Scholar
  35. Wilschut J, Scholma J, Eastman SJ, Hope MJ, Cullis PR (1992) Ca2+-induced fusion of phospholipid vesicles containing free fatty acids: modulation by transmembrane pH gradients. Biochemistry 31:2629–2636PubMedCrossRefGoogle Scholar
  36. Wojtczak L, Schönfeld P (1993) Effect of fatty acids on energy coupling processes in mitochondria. Biochim Biophys Acta 1183:41–57PubMedCrossRefGoogle Scholar

Copyright information

© European Biophysical Societies' Association 2014

Authors and Affiliations

  • Mikhail V. Dubinin
    • 1
    • 2
    Email author
  • Victor N. Samartsev
    • 1
  • Maxim E. Astashev
    • 2
    • 3
  • Alexey S. Kazakov
    • 4
  • Konstantin N. Belosludtsev
    • 2
  1. 1.Mari State UniversityYoshkar-OlaRussia
  2. 2.Institute of Theoretical and Experimental Biophysics RASPushchinoRussia
  3. 3.Institute of Cell Biophysics RASPushchinoRussia
  4. 4.Institute for Biological Instrumentation RASPushchinoRussia

Personalised recommendations