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Cytochrome c–cardiolipin complex in a nonpolar environment

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Abstract

Programmed cell death (apoptosis) plays an important role in the life of multicellular organisms and in the development of socially significant human diseases. Cytochrome c–cardiolipin complex (Cyt-CL) is formed at the very beginning of a cascade of apoptotic reactions. Nevertheless, the structure of the complex and the mechanism of its participation in lipid peroxidation in mitochondrial membranes are not yet understood. In previous work (Vladimirov, Y. A., et al. (2011) Crystallography, 56, 712-719), it was shown that the Cyt-CL complex precipitates in concentrated water solution, the sediment containing orderly nanospheres formed by cytochrome c molecules with changed conformation and surrounded by a cardiolipin monolayer, and they are essentially hydrophobic. In this work, we obtained chloroform and hexane solutions of Cyt-CL with lipid/protein ratio of 77 ± 11. The conditions are described under which the solutions were obtained. Study of the properties of Cyt-CL solutions in hydrophobic media will reveal their structure and the mechanism of their catalytic activity inside the lipid layer of biological membranes.

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Abbreviations

Cyt-CL:

cytochrome c-cardiolipin complex

TOCL:

1,1′,2,2′-tetraoleoylcardiolipin

References

  1. Kagan, V. E., Tyurin, V. A., Jiang, J., Tyurina, Y. Y., Ritov, V. B., Amoscato, A. A., Osipov, A. N., Belikova, N. A., Kapralov, A. A., Kini, V. V., Vlasova, I. I., Zhao, Q., Zou, M., Di, P., Svistunenko, D. A., Kurnikov, I. V., and Borisenko, G. G. (2005) Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors, Nature Chem. Biol., 1, 223–232.

    Article  CAS  Google Scholar 

  2. Kagan, V. E., Bayir, H. A., Belikova, N. A., Kapralov, A. A., Tyurina, Y. Y., Tyurin, V. A., Jiang, J., Stoyanovsky, D. A., Wipf, P., Kochanek, P. M., Greenberger, J. S., Pitt, B., Shvedova, A. A., and Borisenko, G. G. (2009) Cytochrome c/cardiolipin relations in mitochondria: a kiss of death, Free Radic. Biol. Med., 46, 1439–1453.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Zhivotovsky, B., Orrenius, S., Brustugun, O. T., and Doskeland, S. O. (1998) Injected cytochrome c induces apoptosis, Natur., 391, 449–450.

    Article  CAS  Google Scholar 

  4. Skulachev, V. P. (1998) Cytochrome c in the apoptotic and antioxidant cascades, FEBS Lett., 423, 275–280.

    Article  CAS  PubMed  Google Scholar 

  5. Skulachev, V. P. (1996) Why are mitochondria involved in apoptosis? Permeability transition pores and apoptosis as selective mechanisms to eliminate superoxide-producing mitochondria and cell, FEBS Lett., 397, 7–10.

    Article  CAS  PubMed  Google Scholar 

  6. Skulachev, V. P. (2000) How proapoptotic proteins can escape from mitochondria? Free Radic. Biol. Med., 29, 1056–1059.

    Article  CAS  Google Scholar 

  7. Vladimirov, Y. A. (2002) Impairment of the barrier properties of the inner and outer mitochondrial membranes, necrosis and apoptosis, Biol. Membr. (Moscow), 19, 356–377.

    CAS  Google Scholar 

  8. Vladimirov, Y. A., Proskurnina, E. V., Izmailov, D. Y., Novikov, A. A., Brusnichkin, A. V., Osipov, A. N., and Kagan, V. E. (2006) Mechanism of activation of cytochrome c perox-idase activity by cardiolipin, Biochemistr., 91, 989–997.

    Google Scholar 

  9. Belikova, N. A., Vladimirov, Y. A., Osipov, A. N., Kapralov, A. A., Tyurin, V. A., Potapovich, M. V., Basova, L. V., Peterson, J., Kurnikov, I. V., and Kagan, V. E. (2006) Per-oxidase activity and structural transitions of cytochrome c bound to cardiolipin-containing membranes, Biochemistr., 45, 4998–5009.

    Article  CAS  Google Scholar 

  10. Vladimirov, Y. A., Proskurnina, E. V., and Alekseev, A. V. (2013) Molecular mechanisms of apoptosis. Structure of cytochrome c–cardiolipin complex, Biochemistry (Moscow., 78, 1086–1097.

    Article  CAS  Google Scholar 

  11. Papahadjopoulos, D., and Miller, N. (1967) Phospholipid model membranes. I. Structural characteristics of hydrated liquid crystals, Biochim. Biophys. Act., 135, 624–638.

    Article  CAS  Google Scholar 

  12. Shipley, G. G., Leslie, R. B., and Chapman, D. (1969) X-Ray diffraction study of the interaction of phospholipids with cytochrome c in the aqueous phase, Natur., 222, 561–562.

    Article  CAS  Google Scholar 

  13. Shipley, G. G., Leslie, R. B., and Chapman, D. (1969) Small-angle X-ray scattering studies of cytochrome c–phos-pholipid complexes, Biochim. Biophys. Act., 173, 1–10.

    Article  CAS  Google Scholar 

  14. Quinn, P. J., and Dawson, R. M. (1969) The interaction of cytochrome c with monolayers of phosphatidylethanolamine, Biochem. J., 113, 791–803.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Brown, L. R., and Wuthrich, K. (1977) A spin label study of lipid oxidation catalyzed by heme proteins, Biochim. Biophys. Act., 464, 356–369.

    Article  CAS  Google Scholar 

  16. Brown, L. R., and Wuthrich, K. (1977) NMR and ESR studies of the interactions of cytochrome c with mixed car-diolipin–phosphatidylcholine vesicles, Biochim. Biophys. Act., 468, 389–410.

    Article  CAS  Google Scholar 

  17. De Jongh, H. H., Ritsema, T., and Killian, J. A. (1995) Lipid specificity for membrane mediated partial unfolding of cytochrome c, FEBS Lett., 360, 255–260.

    Article  PubMed  Google Scholar 

  18. Lee, I., Salomon, A. R., Yu, K., Doan, J. W., Grossman, L. I., and Huttemann, M. (2006) New prospects for an old enzyme: mammalian cytochrome c is tyrosine-phosphory-lated in vivo, Biochemistr., 45, 9121–9128.

    Article  CAS  Google Scholar 

  19. Nantes, I. L., Faljoni-Alario, A., Vercesi, A. E., Santos, K. E., and Bechara, E. J. (1998) Liposome effect on the cytochrome c-catalyzed peroxidation of carbonyl substrates to triplet species, Free Radic. Biol. Med., 25, 546–553.

    Article  CAS  PubMed  Google Scholar 

  20. Sinibaldi, F., Fiorucci, L., Patriarca, A., Lauceri, R., Ferri, T., Coletta, M., and Santucci, R. (2008) Insights into cytochrome c–cardiolipin interaction. Role played by ionic strength, Biochemistr., 47, 6928–6935.

    Article  CAS  Google Scholar 

  21. Nantes, I. L., Zucchi, M. R., Nascimento, O. R., and Faljoni-Alario, A. (2001) Effect of heme iron valence state on the conformation of cytochrome c and its association with membrane interfaces. A CD and EPR investigation, J. Biol. Chem., 276, 153–158.

    Article  CAS  PubMed  Google Scholar 

  22. Letellier, L., and Shechter, E. (1973) Correlations between structure and spectroscopic properties in membrane model sys-tem. Fluorescence and circular dichroism of the cytochrome c–cardiolipin system, Eur. J. Biochem., 40, 507–512.

    Article  CAS  PubMed  Google Scholar 

  23. Kapralov, A. A., Yanamala, N., Tyurina, Y. Y., Castro, L., Samhan-Arias, A., Vladimirov, Y. A., Maeda, A., Weitz, A. A., Peterson, J., Mylnikov, D., Demicheli, V., Tortora, V., Klein-Seetharaman, J., Radi, R., and Kagan, V. E. (2011) Topography of tyrosine residues and their involvement in peroxidation of polyunsaturated cardiolipin in cytochrome c/cardiolipin peroxidase complexes, Biochim. Biophys. Act., 1808, 2147–2155.

    Article  CAS  Google Scholar 

  24. Heimburg, T., and Marsh, D. (1993) Investigation of sec-ondary and tertiary structural changes of cytochrome c in complexes with anionic lipids using amide hydrogen exchange measurements: an FTIR study, Biophys. J., 65, 2408–2417.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Kagan, V. E., Borisenko, G. G., Tyurina, Y. Y., Tyurin, V. A., Jiang, J., Potapovich, A. I., Kini, V., Amoscato, A. A., and Fujii, Y. (2004) Oxidative lipidomics of apoptosis: redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine, Free Radic. Biol. Med., 37, 1963–1985.

    Article  CAS  PubMed  Google Scholar 

  26. Bayir, H., Fadeel, B., Palladino, M. J., Witasp, E., Kurnikov, I. V., Tyurina, Y. Y., Tyurin, V. A., Amoscato, A. A., Jiang, J., Kochanek, P. M., DeKosky, S. T., Greenberger, J. S., Shvedova, A. A., and Kagan, V. E. (2006) Apoptotic interactions of cytochrome c: redox flirt-ing with anionic phospholipids within and outside of mito-chondria, Biochim. Biophys. Act., 1757, 648–659.

    Article  CAS  Google Scholar 

  27. Kagan, V. E., Tyurina, Y. Y., Bayir, H., Chu, C. T., Kapralov, A. A., Vlasova, I. I., Belikova, N. A., Tyurin, V. A., Amoscato, A., Epperly, M., Greenberger, J., Dekosky, S., Shvedova, A. A., and Jiang, J. (2006) The “pro-apop-totic genies” get out of mitochondria: oxidative lipidomics and redox activity of cytochrome c/cardiolipin complexes, Chem.-Biol. Interact., 163, 15–28.

    Article  CAS  PubMed  Google Scholar 

  28. Kagan, V. E., Wipf, P., Stoyanovsky, D., Greenberger, J. S., Borisenko, G. G., Belikova, N. A., Yanamala, N., Samhan Arias, A. K., Tungekar, M. A., Jiang, J., Tyurina, Y. Y., Ji, J., Klein-Seetharaman, J., Pitt, B. R., Shvedova, A. A., and Bayir, H. (2009) Mitochondrial targeting of electron scav-enging antioxidants: regulation of selective oxidation vs ran-dom chain reactions, Adv. Drug Deliv. Rev., 61, 1375–1385.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Huttemann, M., Pecina, P., Rainbolt, M., Sanderson, T. H., Kagan, V. E., Samavati, L., Doan, J. W., and Lee, I. (2011) The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from res-piration to apoptosis, Mitochondrio., 11, 369–381.

    Article  Google Scholar 

  30. Beales, P. A., Bergstrom, C. L., Geerts, N., Groves, J. T., and Vanderlick, T. K. (2011) Single vesicle observations of the cardiolipin–cytochrome c interaction: induction of membrane morphology changes, Langmui., 27, 6107–6115.

    Article  CAS  Google Scholar 

  31. Vladimirov, Y. A., Nohl, J. Z., and Volkov, V. V. (2011) Protein–lipid nanoparticles responsible for the life or death of living cell, Crystallograph., 56, 712–719.

    Google Scholar 

  32. Das, M. L., Haak, E. D., and Crane, F. L. (1965) Proteolipids. IV. Formation of complexes between cytochrome c and puri-fied phospholipids, Biochemistr., 4, 859–865.

    Article  CAS  Google Scholar 

  33. Folch, J., Lees, M., and Sloane Stanley, G. H. (1957) A simple method for the isolation and purification of total lipides from animal tissues, J. Biol. Chem., 226, 497–509.

    CAS  PubMed  Google Scholar 

  34. Jain, R., Sharma, D., and Kumar, R. (2013) Effects of alcohols on the stability and low-frequency local motions that control the slow changes in structural dynamics of fer-rocytochrome c, J. Biochem., 154, 341–354.

    Article  CAS  PubMed  Google Scholar 

  35. Alekseev, A. V. (2014) The Structure and Function of the Cytochrome c–Cardiolipin Complex: Ph. D. Thesis on Biological Sciences [in Russian], Moscow State University Publishers, Moscow.

    Google Scholar 

  36. De Kruijff, B., and Cullis, P. R. (1980) Cytochrome c specifically induces non-bilayer structures in cardiolipin-containing model membranes, Biochim. Biophys. Act., 602, 477–490.

    Article  CAS  Google Scholar 

  37. Bergstrom, C. L., Beales, P. A., Lv, Y., Vanderlick, T. K., and Groves, J. T. (2013) Cytochrome c causes pore forma-tion in cardiolipin-containing membranes, Proc. Natl. Acad. Sci. USA., 110, 6269–6274.

    Article  PubMed Central  PubMed  Google Scholar 

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Correspondence to Yu. A. Vladimirov.

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Original Russian Text © A. S. Vikulina, A. V. Alekseev, E. V. Proskurnina, Yu. A. Vladimirov, 2015, published in Biokhimiya, 2015, Vol. 80, No. 10, pp. 1572-1577.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM15-157, August 23, 2015.

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Vikulina, A.S., Alekseev, A.V., Proskurnina, E.V. et al. Cytochrome c–cardiolipin complex in a nonpolar environment. Biochemistry Moscow 80, 1298–1302 (2015). https://doi.org/10.1134/S0006297915100107

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  • DOI: https://doi.org/10.1134/S0006297915100107

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