The Sesaki 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, the lab has identified several components that mediate and regulate mitochondrial fusion. The lab is currently trying to determine their functions in both yeast and mammals. The goals of this research are to understand the molecular basis of mitochondrial fusion using biochemical approaches and to determine the physiological roles of mitochondrial fusion using cell culture and animal models.
Lab Website: Sesaki Lab
Adachi, Y. and Sesaki, H. "Cyclin C: An inducer of mitochondrial division hidden in the nucleus." Developmental Cell. 28: 112-114. 2014.
Richter, V., Palmer, C.S., Osellame, J.D., Singh, A. P., Elgass, K., Stroud, D.A., Sesaki, H., Kvansakul, M., and Ryan, M.T. "Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission." J. Cell Biol. 204: 477-486. 2014.
Itoh, K., Tamura, Y., Iijima, M., and Sesaki H. "Effects of Fcj1-Mos1 and mitochondrial division on aggregation of mitochondrial DNA nucleoids and organelle morphology." Mol. Biol. Cell. 24: 1842-1851. 2013.
Sesaki, H., Adachi, Y., Kageyama, Y., Itoh, K., and Iijima, M. "In vivo functions of Drp1: Lessons learned from yeast genetics and mouse knockouts." Biochim Biophys Acta. Epub ahead of print. 2013.
Clerc, P., Ge, S.X., Hwang, H., Waddell, J., Roelofs, B.A., Karbowski, M., Sesaki, H., and Polster, B.M. "Drp1 is dispensable for apoptotic cytochrome c release in primed MCF10A and fibroblast cells but affects Bcl-2 antagonist-induced respiratory changes." Br. J. Pharmacol. Epub ahead of print. 2013.