Immo E. Scheffler
Professor of Biology, UCSD

e-mail: ischeffler@ucsd.edu
Lab Homepage: Scheffler Lab

    After 35 years of operation the Scheffler laboratory was closed in 2006.

    I continue to be interested in all aspects of mitochondrial biology, with emphasis on the biogenesis of the electron transport chain and the regulation of oxidative phosphorylation. Our focus is on complex I (NADH-CoQ oxidoreductase), and on complex II of the electron transport chain which includes succinate dehydrogenase.
    
    There are on-going collaborations with laboratories at UCSD, at UC Irvine, and at a medical school in Southport, Australia. Work at UCI (D. Wallace) is concerned with one of our Chinese hamster cell mutants complemented by an as yet unidentified X-linked gene. The genes for the known 45 subunits of complex I have all been mapped and sequenced in humans. One of our goals is to identify this gene which is hypothesized to encode an essential assembly factor. Interest in this postulated gene is high, because a large fraction of human patients (mostly males) with a mitochondrial disease have a complex I deficiency. However, analysis of all the known genes in these patients has failed to reveal a mutation. At UCSD (S. Taylor) the interest is in the role of protein phosphorylation in mitochondria. Some of the subunits of complex I have been shown to be phosphorylated in vitro, and we have investigated these subunits after site-directed mutagenesis and expression in some of our hamster mutant cell lines. The interest of the Australian group is in apoptosis and the role of reactive oxygen species generated by complex II in the presence of specific inhibitors.

    During the past six months much effort has been devoted to the writing of a new edition of my book, MITOCHONDRIA. After the success of the first edition (1999), the publisher (J. Wiley) invited me to write an updated second edition.

     N. Yadava, P. Potluri , and I.E. Scheffler (2007). Phosphorylation of NADH ubiquinone oxidoreductase (complex I) in fibroblast mitochondria. In preparation.
 
     Scheffler, I.E. 1999. MITOCHONDRIA. J. Wiley and Sons, New York. 364 pages. Second Edition in preparation for 2007.
 
     J. Neuzil, J.C.Dyason, R.E. Freeman, I.E Scheffler, S. J. Ralph  (2007). Vitamin E analogues inhibiting complex II as examples of Mitocans: anti-cancer compounds targeting mitochondria. In press. 
 
     I. E. Scheffler (2007). Basic Molecular Biology of Mitochondrial Replication. Invited review for a book entitled Mitochondrial Dysfunction in Drug-Induced Toxicity. Eds. Y. Will and J.A. Dykens. John Wiley and Sons.
 
     Broderick, K.E., Potluri, P., Zhuang,S., Scheffler, I.E., Sharma, V.S., Pilz, R.B., and G.R. Boss (2006). Cyanide detoxification by the cobalamine precursor cobinamide. Exp. Biology and Medicine. 231: 641-649.

     I. E. Scheffler , N. Yadava, and P. Potluri. (2004). Molecular Genetics of Complex I-Deficient Chinese Hamster Cell Lines. Biochem. Biophys. Acta. 1659: 160 - 171.

     Ricci, J.-E., Munoz-Pinedo, C., Fitzgerald, P., Bailly-Maitre, B., Perkins, G.A., Yadava, N., Scheffler, I.E ., Ellisman, M.H., and Green, D.R. (2004). Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit (NDUSF1) of complex I of the electron transport chain. CELL 117: 1-20.

     Scheffler, I. E. (2004). The Human OXPHOS system: Structure, Function, Physiology. Chapter 1 in Oxidative Phosphorylation in Health and Disease. J.A.M. Smeitink, R.C.A. Sengers, J.M. F. Trijbels, editors. Landes Bioscience and Kluwer Academic/Plenum Publishers.

     N. Yadava, T. Houchens, P. Potluri, and I. E. Scheffler (2004). Development and Characterization of a Conditional Mitochondrial Complex I Assembly System. J. Biol. Chem. 279: 12406 - 12413.

     N. Yadava, I. E. Scheffler (2004). Import and orientation of the MWFE protein in mitochondrial NADH-ubiquinone oxidoreductase. Mitochondrion 4: 1-12 .

     P. Potluri, N. Yadava and I. E. Scheffler. (2004). The role of the ESSS protein in the assembly of a functional and stable mammalian mitochondrial complex I (NADH-ubiquinone oxidoreductase). Eur. J. Biochem. 271: 3264 - 3273.

     Scheffler, I.E. (2003). Mitochondrial dysfunction in genetic diseases. Chapt. 11 in Redox-Genome Interactions in Health and Disease. (Fuchs, ed). Marcel Dekker, Inc. New York, N.Y.

     Albayrak, T., Schoenfeld, N., Brazilius, E., Mund, T., Scherhammer, V., Bauer, M.K.A., Scheffler, I.E., and S. Grimm (2003). Complex II of the respiratory chain is a sensor for drug-induced apoptosis: identification by a screen for proapototic genes. Molec. Biol. Cell. 14: 3082-3096.

     Yadava, N., Potluri, P., Smith, E.N., Bisevac, A., and Scheffler, I.E. (2002). Species-specific and mutant MWFE proteins: their effect on the assembly of a functional mammalian mitochondrial complex I. J. Biol. Chem. 277: 21221-21230.

After receiving his Ph.D. from Stanford University, Immo Scheffler was a Helen Hay Whitney Fellow at Harvard University and the Pasteur Institute, Paris. He is the recipient of an Alexander von Humbolt Award for Senior U.S. Scientists. At UCSD, Professor Scheffler has been honored with a Chancellor's Associates Excellence in Teaching Award, an Alumni Association Teacher of the Year Award, and a teaching award from the Academic Senate. Professor Scheffler was the first holder of the Paul D. Saltman Chair in Science Education at UCSD (2001-2004).  Editorial boards include the Journal of Biological Chemistry.