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BCMBJHU SOM

Faculty & Research

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Hiromi Sesaki

Department Affiliation Primary: Cell Biology
RankAssociate Professor
Phone Numbers
Lab: 410-502-6842
Emailhsesaki@jhmi.edu
School of Medicine Address725 N. Wolfe St.
Hunterian 105/111
Baltimore MD 21205
Link to Lab Homepage
Hiromi Sesaki

Research Topic: Molecular Mechanisms and Physiological Roles of Mitochondrial Fusion and Division

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:

Kageyama, Y., Zhang, Z., and Sesaki, H. (2011). Mitochondrial division: molecular machinery and physiological functions. Curr. Opin. Cell Biol. In press.
PubMed Reference

Zhang, Z., Wakabayashi, N., Wakabayashi, J., Tamura, Y., Song, W.-J., Sereda, S., Clerc, P., Polster, B.M., Aja, S.M., Pletnikov, M.V., Kensler, T.W., Shirihai, O.S., Iijima, M., Hussain, M., and Sesaki, H. (2011). The Dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells. Mol. Biol. Cell. 22: 2235-2245.
PubMed Reference
 
Itoh, K., Tamura, Y., and Sesaki, H. (2011). SnapShot: Mitochondrial dynamics. Cell. 145:1158-11581e.
PubMed Reference
 
Wang, Y., Steimle, P.A., Ren, Y., Ross, C.A., Robinson, D.N., Egelhoff, T.T., Sesaki, H., and Iijima, M. (2011). Dictyostelium huntingtin controls chemotaxis and cytokinesis through the regulation of myosin II phosphorylation. Mol. Biol. Cell. 22: 2270-2281.
PubMed Reference
 
Nakamura. K., Nemani, V.M., Azarbal, F., Skibinski, G., Levy, J.M., Egami, K., Munishkina, L., Zhang, J., Gardner, B., Wakabayashi, J., Sesaki, H., Cheng, Y., Finkbeiner, S., Nussbaum,.R.L., Masliah, E., and Edwards, R.H. (2011). Direct membrane association drives mitochondrial fission by the Parkinson Disease-associated protein α-synuclein. J. Biol. Chem. 286: 20710-20726.
PubMed Reference
 
Tamura, Y., Iijima, M., and Sesaki, H. (2010). Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation. EMBO J. 29: 2875-2887.
PubMed Reference
 
Zhang, P., Wang, Y., Sesaki, H. and Iijima, M. (2010). Proteomic identification of PtdIns(3,4,5)P3-binding proteins in D. discoideum. Proc. Natl. Acad. Sci. USA. 107: 11829-11834.
PubMed Reference
 
Wakabayashi, J., Zhang, Z., Wakabayashi, N., Tamura, Y., Fukaya, M., Kensler, T.W., Iijima, M., and Sesaki, H. (2009). The dyanmin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 186: 805-816.
PubMed Reference
 
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.
PubMed Reference
 
Tamura, Y., Harada, Y., Shiota, T., Yamano, K., Watanabe, K., Yokota, M., Yamamoto, H., Sesaki, H., Endo, T. (2009). Tim23-Tim50 pair coordinates functions of translocators and motor proteins in mitochondrial protein import. J. Cell Biol. 184: 129-141.
PubMed Reference
 
Dunn, C.D., Tamura, Y., Sesaki, H., Jensen, R.E. (2008). Mgr3p and Mgr1p are adaptors for the mitochondrial i-AAA protease complex. Mol Biol Cell. 19: 5387-97.
PubMed Reference
 
Cerveny, K.L., Tamura, Y., Zhang, Z., Jensen, R.E., and Sesaki, H. (2007). Regulation of Mitochondrial Fusion and Division. Trend Cell Biol. 17:563-569.
PubMed Reference
 
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.
PubMed Reference
 
Yoshino, R., Morio, T., Yamada, Y., Kuwayama, H., Sameshima, M., Tanaka, Y., Sesaki, H., and Iijima, M. (2007). Regulation of ammonia homeostasis by the ammonium transporter AmtA in Dictyostelium. Eukaryot Cell. 6: 2419-2428.
PubMed Reference
 
Jensen, R.E. and Sesaki, H. (2006). Ahead of the curve: mitochondrial fusion and phospholipase D. Nat. Cell Biol. 8: 1215-1217.
PubMed Reference
 
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.
PubMed Reference
 
Sesaki, H. and Jensen, R.E. (2004). Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. J. Biol. Chem. 279: 28298-28303.
PubMed Reference
 
Jensen, R.E., Dunn, C., Youngman, M. and Sesaki, H. (2004). Mitochondrial building blocks. Trends Cell Biol. 12: 215-218.
Pubmed Reference
 
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.
PubMed Reference
 
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.
PubMed Reference
 
Sesaki, H. and Jensen, R.E. (2001). UGO1 encodes an outer membrane protein required for mitochondrial fusion. J. Cell Biol. 152:1123-34.
PubMed Reference
 
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.
PubMed Reference
 
Sesaki, H. and Jensen, R.E. (1999). Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J. Cell Biol. 147: 699-706.
PubMed Reference​ 
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