The Sesaki laboratory is interested in the molecular mechanisms and physiological roles of mitochondrial fusion and division. Mitochondria are highly dynamic and control their morphology by a balance of fusion and division. The regulation of membrane fusion and division 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 and division using biochemical approaches and to determine the physiological roles of mitochondrial fusion using cell culture and animal models.
Yamada T, Murata D, Adachi Y, Itoh K, Kameoka S, Igarashi A, Kato T, Araki Y, Huganir RL, Dawson TM, Yanagawa T, Okamoto K, Iijima M, Sesaki H. (2018). Mitochondrial stasis reveals p62-mediated ubiquitination in parkin-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 28: 588-604
Adachi Y, Itoh K, Yamada T, Cerveny KL, Suzuki TL, Macdonald P, Frohman MA, Ramachandran R, Iijima M, and Sesaki H. (2016) Coincident phosphatidic acid interaction restrains Drp1 in mitochondrial division. Mol. Cell. 63: 1034-43
Tamura Y, Itoh K, and Sesaki H. (2011). SnapShot: Mitochondrial dynamics. Cell. 145:1158-11581e
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
Senoo H, Kamimura K, Kimura R, Nakajima A, Sawai S, Sesaki H, Iijima M. (2019). Phosphorylated Rho-GDP directly activates mTORC2 Kinase toward AKT through dimerization with Ras-GTP to regulate cell migration. Nat. Cell Biol. 21: 867-878