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214A Anatomy-Chemistry
Building |
Complex I (NADH-quinone oxidoreductase) is the largest transmembrane multi-subunit enzyme in the mitochondrial and bacterial respiratory chain. It transports electrons from NADH to quinone, and simultaneously transfers protons across the membrane to build up electrochemical proton gradient. This subsequently drives ATP synthesis. Complex I is also considered to be a major site for generation of reactive oxygen species (ROS), which may be associated with neurodegenerative diseases, Parkinson’s disease, as well as aging and apoptosis. The major interest of my research group is the unique coupling between the electron transfer and proton pumping mechanism of complex I which covers both bacterial and mitochondrial systems, utilizing a wide range of research strategies, from molecular biology, protein biochemistry, enzymology, in combination with various CW- and pulse electron paramagnetic resonance techniques. We also investigate ROS generation mechanism and its relevance to the above mentioned human diseases. Selected Publications: Ohnishi, T and J.C. Salerno (2005) Conformation-driven and semiquinone-gated proton-pump mechanism in the NADH-ubiquinone oxidoreductase (complex I). FEBS Letters 579:4555-4561 Ohnishi, S.T., T. Ohnishi, S. Muranaka, H. Fujita, H. Kimura, H. Uemura, K. Yoshida, and K. Utsumi. (2005) A possible site of superoxide generation in the complex I segment of rat heart mitochondria. J. Bioenerg. Biomembr. 37:1-15. Nakamaru-Ogiso, E., T. Yano, T. Yagi, and T. Ohnishi (2005) Characterization of the iron-sulfur cluster N7 (N1c) in the Subunit NuoG of the proton-translocating NADH-quinone oxidoreductase from Escherichia coli. J. Biol. Chem. 280:301-307. Ohnishi, T., J.J. Johnson, T. Yano, R. LoBrutto, and W.R. Widger. (2005) Thermodynamic and EPR studies of slow relaxing SQ species in the isolated bovine heart complex I. FEBS Letters. 579: 500-506. Yano, T., W. R. Dunham, and T. Ohnishi (2005) Characterization of the ∆μH+-sensitive SQ species (SQNf) and the interaction with cluster N2: New insight into the energy-coupled electron transfer in complex I. Biochemistry 44:1744-1754. Magnitsky, S., L. Toulokhonova, T. Yano, V.D. Sled, C. Hägerhäll, V.G. Grivennikova, D.S. Burbaev, A.D. Vinogradov and T. Ohnishi (2002) EPR Characterization of ubisemiquinones and iron-sulfur cluster N2, central components of the energy coupling in the NADH-ubiquinone oxidoreductase (complex I) in situ. J. Bioenerg. Biomembr. 34:193-208. Ohnishi, T., C.C. Moser, C.P. Page, P.L. Dutton, T. Yano. (2002) Simple redox-linked proton-transfer design: New insights from structures of quinol-fumarate reductase. Structure with folding and design 8:R23-32. Ohnishi, T. (1998) Iron-sulfur clusters/semiquinones in complex I. Biochim. Biophys. Acta 1364:186-206. Ohnishi, T. and Salerno, J.C. (1982) Fe-S complexes in the mitochondrial electron transport chain, In Iron-Sulfur Proteins, Vol. IV (T.G. Spiro, ed.) Wiley Publishing Co., Inc., New York, pp. 285-327. |
