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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2012; 58(1): 3-12

Cytochrome c as an amplifier of ROS release in mitochondria

O.V. Akopova, L.I. Kolchinskaya, Nosar V.I., Bouryi V.A., Mankovska I.N., V.F. Sagach

    Ин-т физиологии им. А.А.Богомольца НАН Украины, Киев.


The influence of exogenous cytochrome c on reactive oxygen species (ROS) formation and its depen­dence on mitochondrial permeability transition pore (MPTP) opening is studied in rat liver mito­chondria. Fluorescent probe dichlorofluorescein (DCF) was used. It was shown that MPTP activa­tion by increasing concentrations of Ca2+ in the medium results in the increase in mitochondrial ROS production and oxygen consumption, but the decrease in matrix calcium retention, dependent on the amount of added Ca2+. Cytochrome c in the incubation medium does not much influence ROS formation when MPTP opening is blocked by cyclosporine A. However, in the presence of cyto-chrome c MPTP opening is accompanied by dramatic increase in ROS production. Steep rise in DCF fluorescence because of matrix ROS formation is sensitive to MPTP opening and is not resulted from the direct interaction between the probe and cytochrome c outside the mitochondria. To explain obtained data the hypothesis is put forward that MPTP could serve for ROS exchange between the matrix and the medium where heme iron of cytochrome c would act as a catalytic center to enhance ROS production. We suppose that apart of its conventional function, cytochrome c which is not involved in electron transport, could serve in such way as the amplifier of ROS production which in turn would provide a background for the development of apoptosis due to MPTP opening. Key words: mitochondria, Ca2+, mitochondrial permeability transition pore, ROS, cytochrome c.

Keywords: мітохондрії, Ca2+, мітохондріальна пора,активні форми кисню, цитохром c.


  1. Akopova O.V. The role of permeability transition pore in transmembrane Ca2+-exchange in mitochondria //Ukr. Biochim. J. - 2008. - 80, №3. - P.40-47.
  2. Akopova O.V. The influence of ATP-dependent K+-channel opener on the opening of mitochondrial per­meability transition pore in rat liver mitochondria // Ibid. - 2011. - 83, №3. - P.37-47
  3. Beavis A.D. Upper and lower limits of the charge translocation stoichiometry of mitochondrial electron transport //J. Biol. Chem. - 1987. - 262, № 13. -P. 6165-6173.
  4. Brand M.D., Affourtit Ch., Esteves T., Green K., Lambert A.J., Miwa S., Pakay J., Parker N. Mitochon­drial superoxide: production, biological effects, and activation of uncoupling proteins //Free Radical Biol. Med. - 2004. - 37, №6. - P.755-767.
  5. Brookes P.S., Yoon Y., Robothham J.L., Anders M.W., Sheu Sh.-Sh. Calcium, ATP, and ROS: a mitochondrial love-hate triangle //Amer. J. Physiol. - 2004. - 287 -P.C817-C833.
  6. Burkitt M.J., Wardman P. Cytochrome c is a potent catalyst of dichlorofluorescein oxidation: implications for the role of reactive oxygen species in apoptosis // 11Biochem. Biophys. Res. Commun. - 2001. - 282 -P.329-333.
  7. Cai J., Jones D.P. Superoxide in apoptosis. Mitochon­drial generation triggered by cytochrome c loss // J. Biol. Chem. - 1998. - 273. - P.11401-11404.
  8. Costa D.T.A., Quinlan C.L., Andrukhiv A., West I.C., Jaburek M., Garlid K.D. The direct physiological ef­fects of mitoKATP opening on heart mitochondria //Amer. J. Physiol. - 2006. - 290. - P. H406-H415.
  9. 9. Gogvadze V., Robertson J.D., Enoksson M., Zhivo-tovsky B., Orrhenius S. Mitochondrial cytochrome c release may occur by volume-dependent mechanisms not involving permeability transition //Biochem. J. -2004. - 378 - P.213-217.
  10. 10. Hackenbrock C.R. Chemical and physical fixation of isolated mitochondria in low-energy and high-energy states //Proc. Natl. Acad. Sci. USA. - 1968. - 61. -P.598-605.
  11. Halliwell B. Oxidants and human disease: some new concepts //FASEB J. - 1987. - 1, №5. - P.358-364.
  12. Ichas F., Jouaville L.S., Mazat J.-P. Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals //Cell. - 1997. - 89. -P.1145-1153.
  13. Jacobs E.E., Sanadi D.R. Phosphorylation couples to electron transport mediated by high potential electron carriers //Biochim. Biophys. Acta. - 1960. - 38. - P.12-33.
  14. Korshunov S.S., Krasnikov B.F., Pereverzev M.O., Skulachev V.P. The antioxidant functions of cytochrome с //FEBS Lett. - 1999. - 462. - P.192-198.
  15. Korshunov S.S., Skulachev V.P., Starkov A.A. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondia //FEBS Lett. – 1997. – 416 – P.15-18.
  16. Kroemer G., Petit P. , Zamzami N., Vayssiere J.-L., Mignotte B. The biochemistry of programmed cell death //FASEB J. – 1995. – 9. – P. 1277-1287.
  17. Knowles M.K., Guenza M.G., Capaldi R.A., Marcus A.H. Cytoskeletal-assisted dynamics of the mitochon-drial reticulum in living cells //Proc. Natl. Acad. Sci. USA. – 2002. – 99. – P.14772-14777.
  18. Kushnareva Y., Murphy A.N., Andreyev A. Complex I-mediated reactive oxygen species generation: modu­lation by cytochrome c and NAD(P)+ oxidation-reduc­tion state //Biochem. J. – 2002. – 368. – P.545-553.
  19. 19. Lander H.M. An essential role for free radicals in sig­nal transduction //FASEB J. – 1997. – 11. – P.118-124.
  20. 20. Pletjushkina O.Yu., Fetisova E.K., Lyamzaev K.G., Ivanova O.Yu., Domnina L.V., Vysokih M.Yu., Pustovidko A.V., Alekseevsky A.V., Alekseevsky D.A., Vasilyev Yu.M., Murphy M.P., Chernyak B.V., Skulachev V.P. Hydrogen peroxide produced inside mitochondria takes part in cell-to-cell transmission of apoptogenic signal //Biochemistry (Moscow). – 2006. – 71, N1. – P.75-84.
  21. Starkov A.A., Polster B.M., Fiskum G. Regulation of hydrogen peroxide production by calcium and Bax //J. Neurochem. – 2002. – 83. – P.220-228.
  22. Zorov D.B., Juhaszova M., Sollott S. Mitochondrial ROS-induced ROS release: an update and review // Biochim. Biophys. Acta. – 2006. – 1757. – P.509-517.
  23. Zorov D.B., Kobrinsky E., Juhaszova M., Sollott S. Examining intracellular organelle function using fluores­cent probes //Circulat. Res. – 2004. – 95. – P.239-252.

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