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The most cited biological Institute in Russia *

Department of bioenergetics

Department of Bioenergetics is one of the oldest in the Institute. It has been organized in the middle of 60-th simultaneously with the Institute. Academician of RAS, Prof. Vladimir Skulachev was its Head from the beginning till nowadays.

Research areas

Investigation of the role of mitochondria in apoptosis and phenoptosis (programmed death of organism). Studies on the molecular mechanisms of aging and the role of mitochondria in this process. Design of the artificial mitochodrially-addressed antioxidants (derivatives of Plastoquinone), and their application in therapy of pathologies induced by oxidative stress and aging. Investigation in the electrogenic stages in purified complex of Photosystem I and in bacterial chromatophores. Studies using artificial bilayer lipid membranes (BLM). Studies on the mechanism of regulated free (non coupled to ATP synthesis) oxidation in mitochondria and the role of mitochondrial fatty acids.

Research results

  1. Discovery of the membrane-penetrating ions which has been used to disclose “mitochondrial electricity” and to prove Mitchell’s chemiosmotic theory of coupling oxidation and phosphorylation [Skulachev et al.1967, Liberman et al. 1969].

  2. Recently on the basis of the penetrating ions conjugated with chloroplast electron carrier and antioxidant, plastoquinone, named SkQ, has been synthesized. They proved to be drugs effective in therapy of pathologies induced by oxidative stress and aging, including several eye diseases, brain, heart, kidney, skin and bone pathologies of laboratory animals [Skulachev et al. 2009, 2010; Skulachev M.V. et al., 2011]. Clinical trials of SkQ in treatment of the dry eye syndrome are already successfully finished in two Moscow hospitals.

  3. Discovery of the direct electrometric method for measurements of electric potential differences across coupling membranes with 50 nanosecond resolution which allows to follow a single charge movements inside protein molecule inlaid into a membrane (Drachev et al.1974). Direct electrometric method was successfully applied to deciphering the mechanism of work of bacteriorhodopsin, bacterial reaction centers, Photosystem I and II and cytochrome oxidase, terminal enzyme of the respiratory chain of mitochondria and many bacteria.

  4. Principle role of aspartate-96 in proton translocation mechanism of bacteriorhodopsin has been shown [Holz et al.1989]. The novel intermediate of bacteriorhodopsin photocycle called P (another name, N) has been described [Drachev, Kaulen et al., 1986].

  5. A possibility that mitochondria serve a function of intracellular electric cables has been proved experimentally [Amchenkova et al. 1988].

  6. It has been found out that reactive oxygen species (ROS) generation increases not linearly but exponentially following the increase of mitochondrial membrane potential [Korshunov et al, 1997]; concept of the “mild uncoupling” of oxidative phosphorylation preventing danger of ROS production and oxidative stress progressing has been put forward [Skulachev, 1996].

  7. New phenomenon of ROS-induced ROS release was found as a mechanism of amplification in ROS cascade generation by mitochondria [Zorov et al. 2000].

  8. ATP/ADP-antiporter and glutamate-aspartate transporter were shown to participate in the uncoupling effect of fatty acids [Andreyev et al. 1989].

  9. Experimental evidence to prove direct utilization of proton potential for mechanical work: rotation of bacterial flagellum [Glagolev, Skulachev, 1978].

  10. Energetic cycle based on electrogenic Na+ transmembrane circulation was described as an alternative for the Mitchel H+- cycle in some alcalophilic bacteria.

  11. V.P. Skulachev put forward a hypothesis of a programmed aging caused by an increase in the level of mitochondrial ROS. Such a phenomenon is assured to be favorable for evolution of genomes, but counterproductive for individuals. For humans senescence looks as a counterproductive atavism which should be switched off.

Patents obtained by Department

  1. Zorov D.B., Plotnikov E.Yu., Morosanova M.A., Isaev N.K., Pevzner I.B., Khryapenkova T.G., Chupyrkina A.A., Rogacheva N.V. Patent of Russian Federation claim №2425425 “Model test-system to probe the efficiency of inflammation treatment in kidney’s tissue”

  2. Zorov D.B., Sukhih G.T., Plotnikov E.Yu., Kirpatovsky V.I., Kazachenko A.V., Isaev N.K., Khryapenkova T.G., Vasilieva A.K., Zorova L.D., Pevzner I.B., Marey M.V. Patent of Russian Federation claim № 2409373 “Application of litium salts for curation of renal insufficiency”.

  3. «Cryogenic fuel layer, fuel core and method of its formation» Patent of Russian Federation claim N 2001121680 (Yaguzhinsky L.S. with collaborators from other institutes).

Grants and projects

At different years research activities of the Department were supported by different grant projects: President’s program for outstanding young scientists, projects supported by Russian Fund of Basic Research (RFBR), International projects supported by funds RFBR (RFBR-NNIO- Germany; RFBR-GFEN China), Federal programs: “Leading Scientific Schools” and President’s program for outstanding young scientists, “Megaproject on practical application of Skulachev ions” supported by OOO “Mitotech” and Institute of Mitoengineering, Moscow State University. Megaproject coordinates activities of a number of scientific groups in Moscow, S.-Petersburg, Novosibirsk, Voronezh, Rostov, Stockholm (Sweden), Osnabrück (Germany) and Prinston (USA).

At a moment (in 2011) there were following grant projects in the Department:

  • 12 RFBR-projects including RFBR-NNIO and RFBR-ofi-m
  • Federal contract № 14.740.11.0010 and “Megaproject on practical application of Skulachev ions”

International collaboration

There is a wide collaboration with different Universities and Institutes outside Russia in the research activities of the Department. In Stockholm University collaborative program is based on the study of the effects of SkQs on the mouse life-span (Arrhenius Laboratories in the Wenner-Gren Institute, V.P.Skulachev’s Megaproject) and studies of functional genomics and differentiation of cyanobacteria (Institute of Botany, Koksharova O.A.). Institute of Structural Biology, Grenoble, France has a collaborative research with L.S.Yaguzhinsky on the selection of conditions for nucleotide’s transporter dimerization in mitochondria. Mechanisms of cardioprotection and mechanisms of mitochondrial permeability transition are studied by D.B.Zorov in cooperation with National Institutes of Health, National Institutes of Aging, National Center of Herontology (Baltimor, USA) and Medical College of New York (USA).

Prizes

Government reward (V.P.Skulachev, 1976), M.V.Lomonosov Reward of MSU (V.P.Skulachev and other investigators), “Lenin’s Komsomol Reward” (V.P.Skulachev and a group of young scientists Glagolev A.M., Konstantinov A.A., Kaulen A.D., Kozlov I. A., Semenov A.Yu.), Government Reward “Russian Young Scientists” (Muntyan M.S., Ustiyan V., Bloch D.A.(1996);Bogachev A.,Starkov A., Popov V. (1998); Borisov V., Siletsky S. (2001)), Reward of European Academy for Young Scientists (at different years: Avetisyan A., Bertsova Yu., Bogachev A., Borisov V., Rokitskaya T., Starkov A., Siletsky S, Lyamzaev K.), Reward of Russian Biochemical Society for Young Scientists, M.V.Lomonosov Reward of MSU for young scientists, A.D.Kaulen Reward for young scientists, etc.

Educational activities

Researchers of the Department are involved in a wide range of educational activities: lectures, practical trainings with students, seminars in the Departments of Moscow University as well as in different other Moscow Educational Institutes (Moscow Physico-Technical Institute, Moscow Institute of Fine Chemical Technology).

For students (4-th grade level) of the Faculty of Bioengineering and Bioinformatics (FBB) and Faculty of Biology of Moscow University, V.P. Skulachev deliver a lecture course on bioenergetics, A.Ya.Mulkidjanyan present addition 5 annual lectures on molecular bioenergetics and O.V.Demin - a course of lectures “Modeling in System Biology and Biomedicine”. Seminar on biochemistry for students of the same Faculty (FBB, 3-d grade level) is hold by S.A.Siletsky.

For students of Moscow Physico-Technical Institute (3-d grade level) there is annual lecture course on biophysics delivered by L.S.Yaguzhinsky and special course “Structure and Function of Membrane Proteins” by Yu.N.Antonenko. L.S. Yaguzhinsky also presents 3-4 lectures about news in bioenergetics on the Cytology subdepartment of the Biology Faculty, Moscow University.

A range of public seminars are organized by researchers of the Department. Among the most famous are: V.P.Skulachev’s Moscow Seminar on Bioenergetics, A.Yu.Semenov’s seminar of Russian’s Society of Photobiologists, regular (once in two weeks) seminar "Molecular genetics of Cyanobacteria" hold by O.A.Koksharova.

Besides researchers are involved in patronation upon students and Ph.D. students making their diploma and Ph.D. certification research work in the Department. As a rule there are about 15 students and 15 Ph.D. students, mainly from FBB, working in the Department simultaneously. At a moment (in 2011) there were 27 students and 15 Ph.D.students in the Department.

At a period 2006- 2011 18 Ph.D. and 4 Doctor of Science qualifications have been obtained in the Department..

Educational literature at recent years (2009- 2011):

  • Skulachev V.P., Bogachev A.V., Kasparinsky F.O. Membrane Bioenergetics. 2011. Published by MSU, 350 pages. Now is translated to English (Springer-Verlag).

  • Koksharova O.A. Cyanobacterial Cell Division: Genetics, Comparative Genomics and Proteomics. In: Handbook of Cell Proliferation Editors: A.P.Briggs and Jacob A. Coburn. Nova Science Publishers, Inc, 2009,p. 221-263
  • Koksharova O.A. Application of Genetic Tools to Cyanobacterial Biotechnology and Ecology. In: Handbook on Cyanobacteria: Biochemistry, Biotechnology and Applications. Editors: Percy M. Gault and Harris J. Marler. Nova Science Publishers, Inc, 2009, p. 211-232
  • Vyssokikh M.Yu., Zorov S.D., Meshalkina L.E., Muntyan M.S., Sevostyanova I.A., Tikhomirova N.K., Vasilieva A.K. Guidance for a reduced practicum on biochemistry. 2009, Published by MSU, 33 pages.
  • Muntyan M.S., Khitrina L.V., Grabovich M.Yu., Eprinzev A.T. Guidance for determination of energetic characteristics of bacterial and intracellular membranes. Published by VSU, 63 pages.

Laboratories

Selected papers Recent papers
  1. Severin F.F., Severina I.I., Antonenko Y.N., Rokitskaya T.I., Cherepanov D.A., Mokhova E.N., Vyssokikh M.Y., Pustovidko A.V., Markova O.V., Yaguzhinsky L.S., Korshunova G.A., Sumbatyan N.V., Skulachev M.V., Skulachev V.P. (2010) Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore. Proceedings of the National Academy of Sciences of the United States of America, 107 (2): 663-668.

  2. Stelmashook E.V., Isaev N.K., Plotnikov E.Y., Uzbekov R.E., Alieva I.B., Arbeille B., Zorov D.B. (2009) Effect of transitory glucose deprivation on mitochondrial structure and functions in cultured cerebellar granule neurons. Neuroscience Letters, 461 (2): 140-144.

  3. Lobysheva N.V., Tonshin A.A., Selin A.A., Yaguzhinsky L.S., Nartsissov Y.R. (2009) Diversity of neurodegenerative processes in the model of brain cortex tissue ischemia. Neurochemistry International, 54 (5): 322-329.

  4. Roginsky V.A., Tashlitsky V.N., Skulachev V.P. (2009) Chain-breaking antioxidant activity of reduced forms of mitochondria-targeted quinones, a novel type of geroprotectors. Aging-Us, 1 (5): 481-489.

  5. Horner A., Antonenko Y.N., Pohl P. (2009) Coupled Diffusion of Peripherally Bound Peptides along the Outer and Inner Membrane Leaflets. Biophysical Journal, 96 (7): 2689-2695.

  6. Kurashov V.N., Allakhverdiev S.I., Zharmukhamedov S.K., Nagata T., Klimov V.V., Semenov A.Y., Mamedov M.D. (2009) Electrogenic reactions on the donor side of Mn-depleted photosystem II core particles in the presence of MnCl(2) and synthetic trinuclear Mn-complexes. Photobiological Sciences, 8 (2): 162-166.

  7. Zorov D.B., Juhaszova M., Yaniv Y., Nuss H.B., Wang S., Sollott S.J. (2009) Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovascular Research, 83 (2): 213-225.

  8. Missner A., Kugler P., Antonenko Y.N., Pohl P. (2008) Passive transport across bilayer lipid membranes: Overton continues to rule. Proceedings of the National Academy of Sciences of the United States of America, 105 (52): E123-E123.

  9. Bocharova N.A., Sokolov S.S., Knorre D.A., Skulachev V.P., Severin F.F. (2008) Unexpected link between anaphase promoting complex and the toxicity of expanded polyglutamines expressed in yeast. Cell Cycle, 7 (24): 3943-3946.

  10. Rokitskaya T.I., Klishin S.S., Severina I.I., Skulachev V.P., Antonenko Y.N. (2008) Kinetic Analysis of Permeation of Mitochondria-Targeted Antioxidants Across Bilayer Lipid Membranes. Journal of Membrane Biology, 224 (1): 9-19.

  11. Antonenko Y.N., Pohl P. (2008) Microinjection in combination with microfluorimetry to study proton diffusion along phospholipid membranes. European Biophysics Journal with Biophysics Letters, 37 (6): 865-870.

  12. Banciu H.L., Sorokin D.Y., Tourova T.P., Galinski E.A., Muntyan M.S., Kuenen J.G., Muyzer G. (2008) Influence of salts and pH on growth and activity of a novel facultatively alkaliphilic, extremely salt-tolerant, obligately chemolithoautotrophic sufur-oxidizing Gammaproteobacterium Thioalkalibacter halophilus gen. nov., sp nov from South-Western Siberian soda lakes. Extremophiles, 12 (3): 391-404.

  13. Peskov K., Goryanin I., Prank K., Tobin F., Demin O. (2008) Kinetic modeling of ace operon genetic regulation in Escherichia coli. J. Bioinform. Comput. Biol., 6 (5): 933-959.

  14. Chertkova R.V., Sharonov G.V., Feofanov A.V., Bocharova O.V., Latypov R.F., Chernyak B.V., Arseniev A.S., Dolgikh D.A., Kirpichnikov M.P. (2008) Proapoptotic activity of cytochrome c in living cells: effect of K72 substitutions and species differences. Mol. Cell Biochem., 314: 85-93.

  15. Zakharov S.D., Hulleman J.D., Dutseva E.A., Antonenko Y.N., Rochet J.C., Cramer W.A. (2007) Helical alpha-synuclein forms highly conductive ion channels. Biochemistry, 46 (50): 14369-14379.

  16. Koksharova O.A., Klint J., Rasmussen U. (2007) Comparative proteomics of cell division mutants and wild-type of Synechococcus sp strain PCC 7942. Microbiology-Sgm, 153: 2505-2517.

  17. Ross M.F., da Ros T., Blaikie F.H., Prime T.A., Porteous C.M., Severina I.I., Skulachev V.P., Kjaergaard H.G., Smith R.A.J., Murphy M.P. (2006) Accumulation of lipophilic dications by mitochondria and cells. Biochemical Journal, 400: 199-208.

  18. Sobko A.A., Kotova E.A., Antonenko Y.N., Zakharov S.D., Cramer W.A. (2006) Lipid dependence of the channel properties of a colicin E1-lipid toroidal pore. Journal of Biological Chemistry, 281 (20): 14408-14416.

  19. Metelkin E., Goryanin I., Demin O. (2006) Mathematical modeling of mitochondrial adenine nucleotide translocase. Biophysical Journal, 90 (2): 423-432.

  20. Zorov D.B., Kobrinsky E., Juhaszova M., Sollott S.J. (2004) Examining intracellular organelle function using fluorescent probes - From animalcules to quantum dots. Circulation Research, 95 (3): 239-252.