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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.
Selected publications:
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).