DEPARTMENT OF BIOENERGETICS
The Department was organized in 1965, and is headed until present, by Prof. V.P.Skulachev.
The Department includes Laboratory of biologically
free oxidation (Head: Prof. E.N.Mokhova), Laboratory of the structure
and function of mitochondria (Head: Prof. D.B.Zorov), Laboratory of
the structure and function of membranes (Head: Prof. L.S.Yaguzhinsky),
Laboratory of electrogenic photoevents (Head: Prof. A.Yu. Semenov),
Research groups of: Acad., Prof. V.P.Skulachev, Prof. Yu.N.Antonenko,
Prof. L.E.Bakeeva, Ph.D. M.S.Muntyan, Ph.D. B.V.Chernyak, Ph.D. O.V.Demin
Department leading researchers: Sc.D. N.K.Isaev, Sc.D. M.D.Mamedov, Sc.D. L.S.Khailova, Ph.D. M.Yu.Vyssokhih, Ph.D. V.I.Dedukhova, Ph.D. A.V.Avetisyan, Ph.D. A.Sobko, Ph.D. T.I.Rokitskaya, Ph.D. V.B.Saprunova, Ph.D. A.V.Pustovidko, Ph.D. D.Izyumov, Ph.D. K.Lyamzaev. Technicians: O.O.Malakhovskaya (Skulachev’s secretary) and M.L.Domninskaya.
Basic scientific trends of the Department. Studies on the mechanism of regulation and physiological significance of the different ways of activation of free (non coupled to ATP synthesis) oxidation in mitochondria. Investigation of the role of mitochondria in apoptosis and phenoptosis. Studies on the molecular mechanisms of aging and the role of mitochondria in this process. Investigation of the electrogenic stages in working Complex of Photosystem I and bacterial chromatophores. Studies using artificial bilayer lipid membranes (BLM).
Participation in Scientific projects and programs.
Scientific joint program “Integration” in collaboration with Biological
and Medical Departments of MSU and M.V.Shemyakin and Yu.Ovchinnikov Institute
of Bioorganic Chemistry RAS. Federal programs: “Leading Scientific Schools”
and President’s program for outstanding young scientists, projects supported
by Russian Fund of Basic Research (RFBR), philanthropic fund “Paritet”, International
projects supported by funds RFBR (RFBR-Now Netherlands; RFBR-GFEN China),
CRDF, INTAS, ISTC (International Scientific-Technical Center), Ludvig Institute
of Cancer Research, “Moscow grant”.
Among the most important findings published by researchers of the Department, one can mention:
Evidence of the protonophore activities of the uncouplers of oxidative phosphorylation (Skulachev et al.1967). Experimental evidence has been found to prove Mitchell’s chemiosmotic theory of coupling oxidation and phosphorylation (Skulachev et al.1967, Liberman et al. 1969). Direct method for measurement of generation of electric potential differences across coupling membranes has been discovered with 50 nanosecond’s resolution which allowed to follow individual charge movements inside protein molecule (Drachev et al.1974). Artificial system octanol-water was proposed to use as a model of biological membranes (Yaguzhinsky et al. 1976). Concept based on experimental evidence proved direct utilization of proton potential for mechanical work (Glagolev, Skulachev 1978). Bacteria were shown to contain chemotaxis system coupled to proton pumps activity (Baryshev et al.1981). D.B.Zorov and L.E.Bakeeva (in collaboration with Yu.S.Chentsov) proved postulated earlier possibility that mitochondria serve a function of intracellular electric cables (Amchenkova et al. 1988, Skulachev 2001). Principle role of aspartate-96 in proton translocation mechanism of bacteriorhodopsin has been investigated (Holz et al.1989). ATP/ADP-antiporter and glutamate-aspartate transporter were shown to participate in the uncoupling effect of fatty acids (Andreyev et al. 1989). Channel activity of benzodiazepine receptor was registered for the first time and associated with mitochondrial permeability transition (Kinnaly et al.1993). Bacteriorhodopsin was shown to take part in photoreception in halobacteria (Bibikov et al. 1993). New phenomenon of ROS-induced ROS release was found as a fundamental mechanism of amplification in ROS cascade generation by mitochondria (Zorov et al.2000). Participation of exogenous quinones in functioning of Photosystem I was proved experimentally (Semenov et al. 2000). Surface membrane potential was shown to be principal for development of toxicity (Zakharov et al. 2002). A new family of fluorescent proteins have been introduced permitting to follow the intracellular traffic of proteins and organelles (Chudakov et al., 2003). A signaling cascade involved in the ischemic preconditioning has been deciphered to be a most perfect natural system of cardiac protection against ischemia (Juhaszova et al., 2004). Recently V.P.Skulachev put forward a new principe assuming existence of the special mechanisms of self-elimination of complicated biological systems (from organells to organisms), switching on when functioning of these systems deviates from the determined genetic program. In particular, generation of the mitochondrial reactive oxygen species (ROS) is involved in such suicide programs. Aging of higher animals is accompanied by an increase in damage induced by mitochondrial ROS. Now it is studied whether scavenging of mitochondrial ROS can slow down the aging programs.in animals.
Scientific rewards: Government reward (V.P.Skulachev), 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 Konstantinov A.A., Kaulen A.D., Kondrashin A., Semenov A.Yu.), Government Reward “Russian Young Scientists” (Muntyan M.S., Ustiyan V., Bloch D.A.(1996)), Reward of Russian Biochemical Society for Young Scientists, M.V.Lomonosov Reward of MSU for young scientists, A.D.Kaulen Reward for young scientists.
1. Skulachev V.P., A.A.Sharaf, Liberman E.A. Proton conductors in the respiratory chain and artificial membranes. Nature. 1967;216:718-19.
2. Liberman E.A., Topali V.F, Tsofina L.M., Skulachev V.P., Jasaitis A.A. Mechanisms of coupling of oxidative phosphorylation and the membrane potential of mitochondria. Nature. 1969;222: 1076-88 3. Drachev L.A., Jasaitis A.A., Kaulen A.D., Kondrashin A.A., Liberman E.A., Nemecek I.B., Ostroumov S.A., Semenov A.Yu., Skulachev V.P. Direct mesurement of electric current generation by cytochrome oxidase. H+-ATPase and bacteriorhodopsin. Nature. 1974; 249: 321-24
4. Yaguzhinsky L.S. Rakhmaninova A.B., Volkov A.A., Boguslavsky L.I. Syntesis of ATP, coupled with action of membrane protonic pumps of the octane/water interphase. Nature.1976; 259: 494-97
5. Glagolev A.N. Skulachev V.P. The proton pump is a molecular engine of motile bacteria. Nature. 1978; 272: 280-82
6. Baryshev V.A., Glagolev A.N. Skulachev V.P. Sensing of DmH in phototaxis of Halobacterium halobium. Nature. 1981; 292: 338-40
7. Zorov, D.B. Coupling membranes as energy-transmitting cables. Filamentous mitochondria in fibroblasts and mitochondrial clusters in cardiomyocytes. J.Cell.Biol.. 1988; 107:481-95.
8. Holz M., Drachev L.A., Mogi T., Otto H., Kaulen A.D., Heyn M.P., Skulachev V.P. Khorana H.G. The Asp-96-> Asn mutation of bacteriorhodopsin slows down the decay of M and the reprotonation phase of the charge translocation. Proc. Natl. Acad. Sci. USA. 1989; 86: 2167-71.
9. Andreyev AYu, Bondareva TO, Dedukhova VI, Mokhova EN, Skulachev VP, Tsofina LM, Volkov NI, Vygodina TV.. The ATP/ADP-antiporter is involved in the uncoupling effect of fatty acids on mitochondria. Eur J Biochem. 1989; 182(3):585-92.
10. Kinnally, K.W., Zorov, D.B., Antonenko, Yu.N., Snyder, S.H., McEnery, M.W., Tedeschi, H. Mitochondrial benzodiazepine receptor linked to inner membrane channels by nanomolar actions of ligands. Proc. Natl. Acad. Sci. USA 1993;90: 1374-78
11. Bibikov S.I., Grishanin R.N., Kaulen A.D., Marwan W., Oesterhelt D., Skulachev V.P. (1993) Bacteriorhodopsin is involved in halobacterial photoreception. Proc. Natl.Acad. Sci. USA 1993; 90:9446-50
12. Skulachev V.P. Mitochondrial filaments and clusters as intracellular power-transmitting cables. Trends Biochem Sci. 2001; 26: 23-9
13. Semenov AY, Vassiliev I.R., van Der Est A, Mamedov MD, Zybailov B, Shen G, Stehlik D, Diner BA, Chitnis PR, Golbeck JH Recruitment of a foreign quinone into the A1 site of photosystem I. Altered kinetics of electron transfer in phylloquinone biosynthetic pathway mutants studied by time-resolved optical, EPR, and electrometric techniques. J Biol Chem. 2000; 275:23429-38.
14. Zorov D.B., Filburn C.R., Klotz L.O., Zweier J.L., Sollott S.J. Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med. 2000;192(7):1001-14
15. Zakharov S.D., Rokitskaya T.I., Shapovalov V.L., Antonenko Y.N., Cramer W.A. Tuning the membrane surface potential for efficient toxin import. Proc. Natl. Acad. Sci. USA 2002; 99: 8654-59
16. Shchepina L.A., Pletjushkina O.Yu., Avetisyan A.V., Bakeeva L.E., Fetisova E.K., Izyumov D.S, Saprunova V.B., Vyssokikh M.Yu., Chernyak B.V. and Skulachev V.P. Oligomycin, inhibitor of F0 part of H+-ATP-synthase, suppresses the TNF-induced apoptosis. Oncogene. 2002; 21: 8149-57
17. Skulachev VP Programmed death phenomena: from organelle to organism. Ann N Y Acad Sci. 2002;959:214-37
18. Chudakov D.M., Belousov V.V., Zaraisky A.G., Novoselov V.V., Staroverov D.B., Zorov D.B., Lukianov S., Lukianov K.A. Kindling fluorescent proteins for precise in vivo photolabeling. Nature Biotechnology.2003; 21: 191-4.
19. Juhaszova M, Zorov D.B., Kim S.H., Pepe S., Fu Q., Fishbein K.W., Ziman B.D., Wang S., Ytrehus K., Antos C.L., Olson E.N., Sollott S..J (2004). Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest. 113(11):1535-49.
20. . Longo, V.D., Mitteldorf, J., Skulachev, V.P. Opinion: programmed and altruistic ageing. Nat Rev Genet. 2005 (11):866-72. Review
Some publications since 2004:
1. Serowy S., Saparov S.M., Antonenko Y.N., Kozlovsky W., Hagen V., Pohl P. Structural proton diffusion along lipid bilayers. Biophys J. 2003; 84:1031 37
2. Kurisu G., Zakharov S.D., Zhalnina M.V., Bano S., Erukova V.Y., Rokitskaya T.I., Antonenko Y.N., Wiener M.C., Cramer W.A. The structure of BtuB with bound colicin E3R-domain implies a translocon. Nat. Struct. Biol. 2003; 10: 948-54
3. Skulachev V.P. Aging and the programmed death phenomena. In: Topics in Current Cenetics, ( Nystrom T. and Osiewacz H.D., Eds.) Model systems in ageing. Springer-Verlag Berlin Heidelberg 2003; 3 191-238
4. Semenov A.Yu., Mamedov M.D., Chamorovsky S.K. Photolectric studies of the transmembrane charge transfer reactions in photosystem I pigment-protein complexes. FEBS Lett. 2003; 553: 223-8. Review
5. Chudakov D.M., Belousov V.V., Zaraisky A.G., Novoselov V.V., Staroverov D.B., Zorov D.B., Lukianov S., Lukianov K.A. Kindling fluorescent proteins for precise in vivo photolabeling. Naure Biotechnology.2003; 21: 191-4.
6.Zorov D.B., Kobrinsky E.Juhaszova M., Sollott S.J. Examining intracellular organelle function using fluorescent probes: from animalcules to quantum dots. . Circ Res. 2004 Aug 6;95(3):239-52.
7. Skulachev V.P., Bakeeva L.E., Chernyak B.V., Domnina L.V., Minin A.A., Pletjushkina O.Y.,Saprunova V.B., Skulachev I.V., Tsyplenkova V.G., Vasiliev J.M., Yaguzhinsky L.S., Zorov D.B. Thread-grain transition of mitochondrial reticulum as a step of mitoptosis and apoptosis. Mol Cell Biochem. 2004;256-257:341-358.
8. Sharonov, GV, Feofanov, AV, Bocharova, OV, Astapova, MV, Dedukhova, VI, Chernyak, BV, Dolgikh, DA, Arseniev, AS, Skulachev, VP, Kirpichnikov, MP. Comparative analysis of proapoptotic activity of cytochrome c mutants in living cells. Apoptosis. 2005,10:797-808.
9. Feniouk, BA, Kozlova, MA, Knorre, DA, Cherepanov, DA, Mulkidjanian, AY, Junge, W. The of ATP synthase: ohmic conductance (10 fS), and absence of voltage gating. Biophys J. 2004, 86:4094-109.
10. Musiani, F, Dikiy, A, Semenov, AY, Ciurli, S. Structure of the intermolecular complex between plastocyanin and cytochrome f from spinach. J Biol Chem. 2005,280:18833-41.
11. Skulachev, V.P., Longo, V.D. Aging as a mitochondria-mediated atavistic program: can aging be switched off? Ann N Y Acad Sci. 2005 Dec;1057:145-64
12. Longo, V.D., Mitteldorf, J., Skulachev, V.P. Opinion: programmed and altruistic ageing. Nat Rev Genet. 2005 Nov;6(11):866-72. Review.
13. Krasnikov, BF, Zorov, DB, Antonenko, YN, Zaspa, AA, Kulikov, IV, Kristal, BS, Cooper, AJ, Brown, AM. Comparative kinetic analysis reveals that inducer-specific ion release precedes the mitochondrial permeability transition. Biochim Biophys Acta. 2005,1708(3):375-92.
14. Juhaszova, M, Rabuel, C, Zorov, DB, Lakatta, EG, Sollott, SJ. Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res. 2005, 66(2):233-44.
15. Skulachev, VP. How to clean the dirtiest place in the cell: cationic antioxidants as intramitochondrial ROS scavengers. IUBMB Life. 2005, 57:305-10. Review.
16. Trubitsin, BV, Ptushenko, VV, Koksharova, OA, Mamedov, MD, Vitukhnovskaya, LA, Grigor'ev, IA, Semenov, AY, Tikhonov, AN. EPR study of electron transport in the cyanobacterium Synechocystis sp. PCC 6803: oxygen-dependent interrelations between photosynthetic and respiratory electron transport chains. Biochim Biophys Acta. 2005,1708(2):238-49.
17. Mulkidjanian, AY, Kozlova, MA, Cherepanov, DA. Ubiquinone reduction in the photosynthetic reaction centre of Rhodobacter sphaeroides: interplay between electron transfer, proton binding and flips of the quinone ring. Biochem Soc Trans. 2005, 33:845-50.
18. Mulkidjanian, AY Ubiquinol oxidation in the cytochrome bc1 complex: reaction mechanism and prevention of short-circuiting. Biochim Biophys Acta. 2005,1709:5-34. Review.
19. Pletjushkina OY, Fetisova EK, Lyamzaev KG, Ivanova OY, Domnina LV, Vyssokikh MY, Pustovidko AV, Vasiliev JM, Murphy MP, Chernyak BV, Skulachev VP. Long-distance apoptotic killing of cells is mediated by hydrogen peroxide in a mitochondrial ROS-dependent fashion. Cell Death Differ. 2005 Nov;12(11):1442-4.
20. Pozniakovsky, AI, Knorre, DA, Markova, OV, Hyman, AA, Skulachev, VP, Severin, FF. Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast. J Cell Biol. 2005, 168:257-69.
«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).