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Primary Faculty  
Hiromi Sesaki, Ph.D.
Associate Professor
Department of Cell Biology
Johns Hopkins University School of Medicine
725 N. Wolfe St., 109 Hunterian
Baltimore, MD 21205
Telephone: 410-502-6842 (Office)
Fax: 410-955-4129
Email: hsesaki@jhmi.edu      

 

 

 

 

 

 

 

 

Research Topic: Mitochondrial Dynamics and Phospholipid Metabolism

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.

 

****Postdoc Positions Are Available****

Selected Publications

Itoh, K., Tamura, Y., Iijima, M., and Sesaki H. (2013). Effects of Fcj1-Mos1 and mitochondrial division on aggregation of mitochondrial DNA nucleoids and organelle morphology. Mol. Biol. Cell. 24: 1842-1851

Tamura, Y., Harada, Y., Nishikawa, S., Yamano, K., Megumi, K., Shiota, T., Kuroda, T., Kuge, O., Sesaki, H., Imai, K., Tomii, K., and Endo, T. (2013). Tam41 is a novel CDP-diacylglycerol synthase for cardiolipin biosynthesis in mitochondria. Cell Metabolism. 17: 709-18.

Yang, Z., Grinchuk, V., Smith, A., Qin, B., Bohl, J., Sun, R., Notari, L., Zhang, Z., Sesaki, H., Urban, J., Shea-Donohue, T., and Zhao, A. (2013). Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity. Infection and Immunity. 81: 1905-1914

Itoh, K., Nakamura, K., Iijima, M., and Sesaki, H. (2013). Mitochondrial dynamics in neurodegeneration. Trends Cell Biol. 23: 64-71

Zhang, Z., Kageyama, Y., and Sesaki, H. (2012). Mitochondrial division prevents neurodegeneration. Autophagy. 8: 1531-1533

Kageyama, Y., Zhang, Z., Roda, R., Fukaya, M., Wakabayashi, J., Wakabayashi, N., Kensler, T.W., Reddy, P.H., Iijima, M. and Sesaki, H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J. Cell Biol. 197(4):535-51.

Tamura, Y., Onguka, O., Itoh, K., Endo, T., Iijima, M., Claypool, S.M., and Sesaki, H. (2012). Phosphatidylethanolamine biosynthesis in mitochondria: phosphatidylserine (PS) trafficking is independent of a PS decarboxylase and intermembrane space proteins, Ups1p and Ups2p. J. Biol. Chem. 287:43961-43971.

Tamura, Y., Onguka, O., Aiken Hobbs, A.E., Jensen, R.E., Iijima, M., Claypool, S.M., and Sesaki, H. (2012). Role for two conserved intermembrane space proteins, Ups1p and Up2p, in intra-mitochondrial phospholipid trafficking. J. Biol. Chem. 287(19):15205-15218.

Trushina, E., Nemutlu, E., Zhang, S., Christensen, T., Camp, J., Mesa, J., Siddiqui, A., Tamura, Y., Sesaki, H., Wengenack, T.M., Poduslo, J., and Dzeja, P. (2012). Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer's disease. PLoS ONE. 7(2): e32737.

Manczak, M., Sesaki, H., Kageyama, Y., and Reddy, P.H. (2012). Dynamin-related protein 1 heterozygote knockout mice do not have synaptic and mitochondrial deficiencies. Biochim Biophys Acta. 1822(6):862-74.

Chen, C-L., Wang, Y., Sesaki, H., and Iijima, M. (2012). Myosin I links PIP3 signaling to remodeling of the actin cytoskeleton in chemotaxis. Science Signaling. 5: ra10

Estela, A., Pla-Martin. D., Sanchez-Piris. M., Sesaki. H., and Palau F. (2011). The Charcot-Marie-Tooth related gene GDAP1 complements cell cycle delay at G2/M in S. cerevisiae fis1 defective cells. J. Biol. Chem. 286: 36777-36786

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.

Kageyama, Y., Zhang, Z., and Sesaki, H. (2011). Mitochondrial division: molecular machinery and physiological functions. Curr. Opin. Cell Biol. 23: 427-34.

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.

Itoh, K., Tamura, Y., and Sesaki, H. (2011). SnapShot: Mitochondrial dynamics. Cell. 145:1158-11581e

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.

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.

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.

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.

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.

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., 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., Jensen, R.E. (2008). Mgr3p and Mgr1p are adaptors for the mitochondrial i-AAA protease complex. Mol Biol Cell. 19: 5387-97.

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.

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.

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.

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.

 

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