Our laboratory is interested in the molecular mechanisms and physiological roles of mitochondrial fusion. Mitochondria are highly dynamic and control their morphology by a balance of fusion and fission. The regulation of membrane fusion and fission generates a striking diversity of mitochondrial shapes, ranging from numerous small spheres in hepatocytes to long branched tubules in myotubes. In addition to shape and number, mitochondrial fusion is critical for normal organelle function. For example, mice that are defective in mitochondrial fusion die during early development while yeast fusion mutants rapidly lose their mitochondria genome and become incapable of oxidative phosphorylation. Moreover, mitochondrial fusion also regulates the release of cytochrome C during apoptosis. Therefore, it is not surprising that defects in mitochondrial fusion cause neurodegenerative disorders in humans, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. Using yeast as a model system, we have identified several components that mediate and regulate mitochondrial fusion. We are currently trying to determine their functions in both yeast and mammals. The goals of our research are to understand the molecular basis of mitochondria fusion using biochemical approaches and to determine the physiological roles of mitochondrial fusion using cell culture and animal models.

Publications:

Tamura, Y., Endo, T., Iijima, M., and Sesaki, H. (2009). Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria. J. Cell Biol. 185: 1029-1045

Tamura, Y., Harada, Y., Shiota, T., Yamano, K., Watanabe, K., Yokota, M., Yamamoto, H., Sesaki, H., and Endo, T. (2009). Tim23-Tim50 pair coordinates functions of translocators and motor proteins in mitochondrial protein import. J. Cell Biol. 184: 129-141

Dunn, C.D., Tamura, Y., Sesaki, H., and Jensen, R.E. (2008). Mgr3p and Mgr1p are adaptors for the mitochondrial i-AAA protease complex . Mol. Biol. Cell. 19: 5387-5397

Cerveny, K.L., Tamura, Y., Zhang, Z., and Jensen, R.E. and Sesaki, H. (2007). Regulation of mitochondrial fusion and division. Trends Cell Biol. 17: 563-569.

Cerveny, K.L., Studer, S.L., Jensen, R.E., and Sesaki, H. (2007). Yeast mitochondrial division and distribution requires the cortical Num1 protein. Dev. Cell. 12:363-375.

Jensen, R.E. and Sesaki, H. (2006). Ahead of the curve: mitochondrial fusion and phospholipase D. Nat. Cell Biol. 8: 1215-1217.

Sesaki, H., Dunn, C.D., Iijima, M., Shepard, K.A., Yaffe, M.P., Machamer, C.E., and Jensen, R.E. (2006). Ups1p, a conserved intermembrane space protein, regulates mitochondrial shape and alternative topogenesis of Mgm1p. J. Cell Biol. 173: 651-658

Sesaki, H. and Jensen, R.E. (2004). Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. J. Biol. Chem. 279: 28298-28303.

Jensen, R.E., Dunn, C., Youngman, M. and Sesaki, H. (2004). Mitochondrial building blocks. Trends Cell Biol. 12: 215-218

Sesaki, H. Southard, S.M, Aiken Hobbs, A.E. and Jensen, R.E. (2003). Cells lacking Pcp1p/Ugo2p, a rhomboid-related protease required for Mgm1p processing, lose mtDNA and mitochondrial structure in a Dnm1p-dependent manner, but remain competent for mitochondrial fusion. Biochem. Biophys. Res. Commun. 308: 276-283.

Sesaki, H., Southard, S.M, Yaffe, M.P., and Jensen, R.E. (2003). Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial outer membrane. Mol. Biol. Cell. 14: 2342-2356.

Sesaki, H. and Jensen, R.E. (2001). UGO1 encodes an outer membrane protein required for mitochondrial fusion. J Cell Biol. 152:1123-34.

Jensen, R.E., Aiken Hobbs, A.E., Cerveny, K. and Sesaki, H. (2000). Yeast mitochondrial dynamics: fusion, division, segregation and shape. Microsc. Res. Tech. 51:573-583

Sesaki, H. and Jensen, R.E. (1999). Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J. Cell Biol. 147: 699-706.