Michael P. Yaffe Professor of Biology, UCSD e-mail: myaffe@ucsd.edu

     Our research is concerned with the inheritance and morphology of subcellular organelles. Most organelles proliferate by growth and division of preexisting organelles, so the transmission of these essential cellular structures to daughter cells is a central feature of cell proliferation. We focus on the behavior of mitochondria, the central organelles of cellular energy metabolism. Our goals are to identify the structures that mediate the positioning of mitochondria within the cell, to characterize the mechanisms that facilitate mitochondrial movement and the maintenance of mitochondrial morphology, and to understand how the process of mitochondrial inheritance is coordinated with other key events of the cell division cycle. 

     Our studies involve a combined genetic and biochemical approach using the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe as model cellular systems. We have isolated a number of yeast mutants which display conditional defects in mitochondrial distribution and morphology (mdm mutants). Our studies of these mutants and wild-type cells employ a variety of experimental approaches including fluorescence and electron microscopy, classical and molecular genetics, biochemical characterization, and immunological analysis. We characterize mutant cells, isolate and analyze genes defined by mdm mutations, and identify and characterize the protein products of these MDM genes. 

     Our investigations have led to the discovery of a number of novel proteins that mediate mitochondrial movement and regulate mitochondrial morphology. Several of these proteins appear to be components of a new cytoskeletal network  that extends throughout the cytoplasm of S.cerevisiae cells and is involved also in nuclear transmission. Other implicated proteins are components of the mitochondrial surface, and these may mediate the interaction of  mitochondria with the cytoskeleton. Recent studies of mitochondrial behavior in the fission yeast S. pombe have  revealed a role for microtubules in this species. Additionally, inheritance components conserved between budding and fission yeast have been identified. 

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     Yaffe, M.P. (1999). The machinery of mitochondrial inheritance and behavior. Science, 283, 1493-1497.

     Fekkes, P., Shepard, K., and Yaffe, M.P. (2000). Gag3p, an outer membrane protein required for fission of mitochondrial tubules. J. Cell Biol. 151, 333-341.

     Yaffe, M.P. (2003). The cutting edge of mitochondrial fusion. Nature Cell Biol., 5, 497- 499.

     Yaffe, M.P., Stuurman, N., and Vale, R.D. (2003). Mitochondrial movement in fission yeast is driven by association with dynamic microtubules and mitotic spindle poles. Proc. Natl. Acad. Sci. USA, 100, 11424-11428.

     Weir, B.A., and Yaffe, M.P. (2004). Mmd1p, a novel, conserved protein essential for normal mitochondrial morphology and distribution in the fission yeast, Schizosaccharomyces pombe. Mole. Biol. Cell, 15, 1656-1665.

     Meisinger, C., Rissler, M., Chacinska, A., Szklarz, L.K., Milenkovic, D., Kozjak, V., Schonfisch, B., Lohaus, C., Meyer, H.E., Yaffe, M.P., Guiard, B., Wiedemann, N., Pfanner, N. (2004). The mitochondrial morphology protein mdm10 functions in assembly of the preprotein translocase of the outer membrane. Dev. Cell, 7, 61-71.

     Malhotra, V., and Yaffe, M.P. (2005). Membranes and organelles: Regulating the size, shape, and plasticity of cellular compartments.Curr. Opin. Cell Biol. 17, 1-2.

     Sesaki, H., Dunn, C.D., Iijima, M., Shepard, K.A., Yaffe, M.P., Machamer, C.E., Jensen, R.E. (2006). Ups1p, a Conserved Intermembrane Space Protein, Regulates Mitochondrial Shape and Alternative Topogenesis of Mgm1p. J. Cell Biol. 173, 651-658.