Welcome to the home page of the "Biological effects of membranophylic cations" laboratory. We are located in Belozersky Research Institute of Physico-Chemical Biology, Moscow State University, Russia.
We study the links between mitochondrial dynamics, reactive oxygen species formation, stress response, and the cell cycle. For this we use the baker’s yeast Saccharomyces cerevisiae as a model organism. We also use yeast to study the mechanism of the toxicity of polyglutamine-driven protein aggregation at cellular level. Our most recent research interest is to apply yeast to study the mechanism of action of penetrating membranophylic cations.
Mitochondria are highly dynamic organelles—they change their shapes according to cellular needs. Normally mitochondria are thread-like structures, while after stresses they fragment and form vesicles. We study the mechanism of the fragmentation and its role in cellular stress response. We have reported the involvement of two proteins, Ysp1 and Ysp2, in the process of stress-induced mitochondrial fragmentation. These proteins were recently found to mediate the transport of ergosterol from the plasma membrane to the endoplasmic reticulum. Currently we are trying to find the links between ergosterol trafficking and mitochondrial stress response.
Penetrating membranophylic cations are widely used as parts of chimeric molecules to deliver various chemicals to mitochondria. We have established two independent activities of the cations: they increase the proton conductivity of the mitochondrial inner membranes and also can inhibit the activity of the plasma membrane multidrug resistance pumps. The latter is due to their property of being recurrent substrates of the pumps. Once extruded, they immediately return into the cell, thus preventing the extrusion of other xenobiotics. This suggests that such compounds can also be used to fight infectious diseases.
Finally, we are interested in one issue which is partly philosophical. On one hand, it was shown that yeast can undergo programmed cell death. On the other hand, there is accumulating evidence that in higher organisms certain types of death including the one induced by senescence might be programmed. As for a unicellular organism programmed cell death means programmed suicide, there is chance for parallels between programmed death of yeast cells and programmed death(s) of multicellular organisms. Our scientific ambition (or should we say “fantasy”?) is to reveal the molecular mechanisms of such ancestral programs.
Severina I.I., Severin F.F., Korshunova G.A., Sumbatyan N.V., Ilyasova T.M., Simonyan R.A., Rogov A.G., Trendeleva T.A., Zvyagilskaya R.A., Dugina V.B., Domnina L.V., Fetisova E.K., Lyamzaev K.G., Vyssokikh M.Y., Chernyak B.V., Skulachev M.V., Skulachev V.P., Sadovnichii V.A. (2013) In search of novel highly active mitochondria-targeted antioxidants: Thymoquinone and its cationic derivatives. FEBS Lett., 587 (13): 2018-2024. >>
Starovoytova A.N., Sorokin M.I., Sokolov S.S., Severin F.F., Knorre D.A. (2013) Mitochondrial signaling in Saccharomyces cerevisiae pseudohyphae formation induced by butanol. FEMS Yeast Res., 13 (4): 367-374. >>
Litvinchuk A.V., Sokolov S.S., Rogov A.G., Markova O.V., Knorre D.A., Severin F.F. (2013) Mitochondrially-encoded protein Var1 promotes loss of respiratory function in Saccharomyces cerevisiae under stressful conditions. Eur. J. Cell Biol., 92 (4): 169-174. >>
Knorre D.A., Popadin K.Y., Sokolov S.S., Severin F.F. (2013) Roles of Mitochondrial Dynamics under Stressful and Normal Conditions in Yeast Cells. Oxidative Med. Cell. Longev., 2013: . >>
Knorre D.A., Severin F.F. (2012) Longevity and mitochondrial membrane potential. Biochem.-Moscow, 77 (7): 793-794. >>
Antonenko Y.N., Avetisyan A.V., Cherepanov D.A., Knorre D.A., Korshunova G.A., Markova O.V., Ojovan S.M., Perevoshchikova I.V., Pustovidko A.V., Rokitskaya T.I., Severina I.I., Simonyan R.A., Smirnova E.A., Sobko A.A., Sumbatyan N.V., Severin F.F., Skulachev V.P. (2011) Derivatives of Rhodamine 19 as Mild Mitochondria-targeted Cationic Uncouplers. Journal of Biological Chemistry, 286 (20): 17831-17840.
Knorre D.A., Smirnova E.A., Markova O.V., Sorokin M.I., Severin F.F. (2011) Prooxidants prevent yeast cell death induced by genotoxic stress. Cell Biology International, 35 (5): 431-435.
Ojovan S.M., Knorre D.A., Markova O.V., Smirnova E.A., Bakeeva L.E., Severin F.F. (2011) Accumulation of dodecyltriphenylphosphonium in mitochondria induces their swelling and ROS-dependent growth inhibition in yeast. Journal of Bioenergetics and Biomembranes, 43 (2): 175-180.
Kochmak S.A., Knorre D.A., Sokolov S.S., Severin F.F. (2011) Physiological Scenarios of Programmed Loss of Mitochondrial DNA Function and Death of Yeast. Biochemistry-Moscow, 76 (2): 167-171.
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.
Knorre D.A., Krivonosova T.N., Markova O.V., Severin F.F. (2009) Amiodarone inhibits multiple drug resistance in yeast Saccharomyces cerevisiae. Archives of Microbiology, 191 (8): 675-679.
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.
Knorre D., Ojovan S., Saprunova V., Sokolov S., Bakeeva L., Severin F. (2008) Mitochondrial matrix fragmentation as a protection mechanism of yeast Saccharomyces cerevisiae. Biochemistry-Moscow, 73 (11): 1254-1259.
Severin F.F., Meer M.V., Smirnova E.A., Knorre D.A., Skulachev V.P. (2008) Natural causes of programmed death of yeast Saccharomyces cerevisiae. Biochimica et Biophysica Acta-Molecular Cell Research, 1783 (7): 1350-1353.
Sokolov S., Knorre D., Smirnova E., Markova O., Pozniakovsky A., Skulachev V., Severin F. (2006) Ysp2 mediates death of yeast induced by amiodarone or intracellular acidification. Biochimica et Biophysica Acta-Bioenergetics, 1757 (9): 1366-1370.
Sokolov S., Pozniakovsky A., Bocharova N., Knorre D., Severin F. (2006) Expression of an expanded polyglutamine domain in yeast causes death with apoptotic markers. Biochimica et Biophysica Acta-Bioenergetics, 1757 (5): 660-666.
Knorre D.A., Smirnova E.A., Severin F.F. (2005) Natural conditions inducing programmed cell death in the yeast Saccharomyces cerevisiae. Biochemistry-Moscow, 70 (2): 264-266.