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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- Cyt-CL:
-
cytochrome c-cardiolipin complex
- TOCL:
-
1,1′,2,2′-tetraoleoylcardiolipin
References
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.
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.
Zhivotovsky, B., Orrenius, S., Brustugun, O. T., and Doskeland, S. O. (1998) Injected cytochrome c induces apoptosis, Natur., 391, 449–450.
Skulachev, V. P. (1998) Cytochrome c in the apoptotic and antioxidant cascades, FEBS Lett., 423, 275–280.
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.
Skulachev, V. P. (2000) How proapoptotic proteins can escape from mitochondria? Free Radic. Biol. Med., 29, 1056–1059.
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.
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.
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.
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.
Papahadjopoulos, D., and Miller, N. (1967) Phospholipid model membranes. I. Structural characteristics of hydrated liquid crystals, Biochim. Biophys. Act., 135, 624–638.
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.
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.
Quinn, P. J., and Dawson, R. M. (1969) The interaction of cytochrome c with monolayers of phosphatidylethanolamine, Biochem. J., 113, 791–803.
Brown, L. R., and Wuthrich, K. (1977) A spin label study of lipid oxidation catalyzed by heme proteins, Biochim. Biophys. Act., 464, 356–369.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
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.
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0006297915100107