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A01-1

ミトコンドリア、ゴルジ体に関連する応答ゾーン、連携ゾーン解析
研究分担者
田村康
山形大学　理学部理学科

研究概要

細胞内に発達したオルガネラがその適切な機能と構造を維持するためには、オルガネラ膜の主成分であるリン脂質組成が適切に保たれる必要があります。このようなオルガネラ膜のリン脂質恒常性維持機構の理解には、小胞体やミトコンドリアで合成されたリン脂質がどのように他のオルガネラ膜へ輸送分配されるのかを知る必要がありますが、リン脂質の細胞内輸送機構についてはほとんど研究されていないのが現状です。私たちは、オルガネラ間リン脂質輸送を仲介するオルガネラゾーン（オルガネラ間コンタクトサイト）に着目し、研究を進めます。具体的にはオルガネラ間コンタクトを検出する実験系の構築、オルガネラテザリング因子の探索と機能解析、さらにはこれらのオルガネラゾーンや、オルガネラテザリング因子がリン脂質輸送に果たす役割の解明を行います。

代表的な原著論文

  1. Matsumoto S., Nakatsukasa K., Kakuta C., Tamura Y., Esaki M., and Endo T. (2019) Msp1 Clears Mistargeted Proteins by Facilitating Their Transfer from Mitochondria to the ER Mol. Cell., 76: 191-205.
  2. Wang C., Taki M., Sato Y., Tamura Y., Yaginuma H., Okada Y., and Yamaguchi S. (2019) A photostable fluorescent marker for the superresolution live imaging of the dynamic structure of the mitochondrial cristae PNAS., 116: 15817-15822.
  3. Sakaue, H., Shiota, T., Ishizaka, N., Kawano, S., Tamura, Y., Tan, KS., Imai, K., Motono, C., Hirokawa, T., Taki, K., Miyata, N., Kuge, O., Lithgow, T., and Endo, T. (2019) Porin Associates with Tom22 to Regulate the Mitochondrial Protein Gate Assembly Mol. Cell, 73, 1044–1055
  4. Sawasato, K., Sato, R., Nishikawa, H., Iimura, N., Kamemoto, Y., Fujikawa, K., Yamaguchi, T., Kuruma, Y., Tamura, Y., Endo, T., Ueda, T., Shimamoto, K. and Nishiyama, K. (2019) CdsA is involved in biosynthesis of glycolipozyme MPIase essential for membrane protein integration in vivo. Sci. Rep., 9, Article number: 1372
  5. Ueda, E., Tamura, Y., Sakaue, H., Kawano, S., Kakuta, C., Matsumoto, S., and Endo, T. (2019) Myristoyl group-aided protein import into the mitochondrial intermembrane space. Sci. Rep., 9, Article number: 1185.
  6. Kojima, R., Kakimoto, Y., Furuta, S., Itoh, K., Sesaki, H., Endo, T., and Tamura, Y. (2019) Maintenance of Cardiolipin and Crista Structure Requires Cooperative Functions of Mitochondrial Dynamics and Phospholipid Transport. Cell Rep., 26, 518–528.
  7. Kawano, S., Tamura, Y., Kojima, R., Bala, S., Asai, E,  Michel, AH., Kornmann, B., Riezman, I., Riezman, H., Sakae, Y., Okamoto, Y., and Endo T. (2017). Structure–function insights into direct lipid transfer between membranes by Mmm1–Mdm12 of ERMES.  J. Cell. Biol. 217, 959–974. DOI: 10.1083/jcb.201704119.
  8. Kojima, R., Endo, T., and Tamura, Y. (2016) A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro. Sci. Rep. 6, Article number: 30777
  9. Watanabe, Y., Tamura, Y., Kawano, S., and Endo T. (2015) Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria. Nat. Commun. 6, Article number: 7922
  10. Tamura, Y., Harada, Y., Nishikawa, S., Yamano, K., Kamiya, M., Shiota, T., Kuroda, T., Kuge, O., Sesaki, H., Imai, K., Tomii, K. and Endo, T. (2013) Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria. Cell Metab., 17, 709-718
  11. 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
  12. 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

総説

  1. Tamura Y. Kawano S. and Endo T*. (2020) Lipid homeostasis in mitochondria. Biol Chem., in press (DOI: 10.1515/hsz-2020-0121.).
  2. Tamura, Y., Kojima, R., Endo, T. (2019) Advanced In Vitro Assay System to Measure Phosphatidylserine and Phosphatidylethanolamine Transport at ER/Mitochondria Interface. In: Drin G. (eds) Intracellular Lipid Transport. Methods Mol. Biol. vol 1949. Humana Press, New York, NY
  3. Tamura, Y., Kawano, S., and Endo T. (2019) Organelle contact zones as sites for lipid transfer. J Biochem. 165, 115–123.
  4. Tamura, Y. and Endo, T. (2017) Role of Intra- and Inter-mitochondrial Membrane Contact Sites in Yeast Phospholipid Biogenesis. In: Tagaya, M., Simmen, T. (eds) Organelle Contact Sites. Adv. Exp. Med. Biol., 997, 121-133, Springer, Singapore
  5. Tamura, Y. Sesaki, H. and Endo, T. (2014) Phospholipid transport via mitochondria. Traffic. 15, 933-945
  6. Zhang, Q., Tamura, Y., Roy, M., Adachi, Y., Iijima, M., Sesaki, H. (2014) Biosynthesis and Roles of Phospholipids in Mitochondrial Fusion, Division and Mitophagy. Cell. Mol. Life Sci. 71, 3767-78