ENGLISH

遺伝子制御学- 遺伝子制御学部門 -


ようこそ山本研究室へ

私たちの研究室では、細胞内の品質管理やリサイクルを担う「オートファジー」の研究を進めており、中でも特定のタンパク質やオルガネラを標的とする「選択的オートファジー」に着目しています。オートファジーは神経変性疾患、がん、細菌感染、初期胚発生など様々な疾患や高次生理機能に関わっていますが、その多くは「選択的オートファジー」に関連するものと考えられます。私たちの研究室では、選択的オートファジーの分子メカニズムについて、個々のタンパク質の機能といったミクロスケールから、タンパク質高次会合体や生体膜といったメゾスケールの機能・構造までシームレスに理解することを目的としており、これをマクロスケールでの疾患発症メカニズムまで展開することでオートファジー関連疾患の診断・予防・治療に繋げたいと考えています。

業績


2022年


  • Ohshima T.*, Yamamoto H.*, Sakamaki Y., Saito C., Mizushima N. (2022) NCOA4 drives ferritin phase separation to facilitate macroferritinophagy and microferritinophagy
    J. Cell Biol., DOI: 10.1083/jcb.202203102
  • Yim W.W., Yamamoto H.*, Mizushima N.* (2022) A HaloTag-based reporter processing assay to monitor autophagic flux
    Autophagy, DOI: 10.1080/15548627.2022.2123638
  • Yim W.W., Yamamoto H.*, Mizushima N.* (2022) A pulse-chasable reporter processing assay for mammalian autophagic flux with HaloTag
    eLife, DOI: 10.7554/eLife.78923
  • Fu J., Pang Y., Chen H., Yamamoto H., Lin Z., Chen Y., Li Z., Mizushima N., Jia H. (2022) Apicoplast biogenesis mediated by ATG8 requires the ATG12–ATG5-ATG16L and SNAP29 complexes in Toxoplasma gondii
    Autophagy, DOI: 10.1080/15548627.2022.2123639
  • Sakamaki J., Ode K.L., Kurikawa Y., Ueda H.R., Yamamoto H., Mizushima N. (2022) Ubiquitination of phosphatidylethanolamine in organellar membranes
    Mol. Cell, DOI: 10.1016/j.molcel.2022.08.008
  • Zhang S., Yazaki E., Sakamoto H., Yamamoto H., Mizushima N. (2022) Evolutionary diversification of the autophagy-related ubiquitin-like conjugation systems
    Autophagy, DOI: 10.1080/15548627.2022.2059168
  • Yim W.W., Yamamoto H., Mizushima N. (2022) Annexins A1 and A2 are recruited to larger lysosomal injuries independently of ESCRTs to promote repair
    FEBS Lett., DOI: 10.1002/1873-3468.14329

2021年


  • Okawa F., Hama Y., Zhang S., Morishita H., Yamamoto H., Levine T.P., Mizushima N. (2021) Evolution and insights into the structure and function of the DedA superfamily containing TMEM41B and VMP1
    J. Cell Sci., DOI: 10.1242/jcs.255877

2020年


  • Maeda S., Yamamoto H., Kinch L.N., Garza C.M., Takahashi S., Otomo C., Grishin N.V., Forli S., Mizushima N., Otomo T. (2020) Structure, lipid scrambling activity and role in autophagosome formation of ATG9A
    Nat. Struct. Mol. Biol., DOI: 10.1038/s41594-020-00520-2

2019年


  • Pang Y.*, Yamamoto H.*, Sakamoto H., Oku M., Mutungi J.K., Sahani M.H., Kurikawa Y., Kita K., Noda N.N., Sakai Y., Jia H., Mizushima N. (2019) Evolution from covalent conjugation to non-covalent interaction in the ubiquitin-like ATG12 system
    Nat. Struct. Mol. Biol., DOI: 10.1038/s41594-019-0204-3
  • Harada K., Kotani T., Kirisako H., Sakoh-Nakatogawa M., Oikawa Y., Kimura Y., Hirano H., Yamamoto H., Ohsumi Y., Nakatogawa H. (2019) Two distinct mechanisms target the autophagy-related E3 complex to the pre-autophagosomal structure
    eLife, DOI: 10.7554/eLife.43088
  • Mizushima N., Matsui T., Yamamoto H. (2019) YKT6 as a second SNARE protein of mammalian autophagosomes
    Autophagy, DOI: 10.1080/15548627.2018.1532262

2018年


  • Matsui T., Jiang P., Nakano S., Sakamaki Y., Yamamoto H., Mizushima N. (2018) Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17
    J. Cell Biol., DOI: 10.1083/jcb.201712058

2017年


  • Tamura N., Nishimura T., Sakamaki Y., Koyama-Honda I., Yamamoto H., Mizushima N. (2017) Differential requirement for ATG2A domains for localization to autophagic membranes and lipid droplets
    FEBS Lett., DOI: 10.1002/1873-3468.12901
  • Uematsu M., Nishimura T., Sakamaki Y., Yamamoto H., Mizushima N. (2017) Accumulation of undegraded autophagosomes by expression of dominant-negative STX17 (syntaxin 17) mutants
    Autophagy, DOI: 10.1080/15548627.2017.1327940
  • Nishimura T., Tamura N., Kono N., Shimanaka Y., Arai H., Yamamoto H., Mizushima N. (2017) Autophagosome formation is initiated at phosphatidylinositol synthase-enriched ER subdomains
    EMBO J., DOI: 10.15252/embj.201695189

2016年


  • Yamamoto H.*, Fujioka Y.*, Suzuki S.W.*, Noshiro D., Suzuki H., Kondo-Kakuta C., Kimura Y., Hirano H., Ando T., Noda N.N., Ohsumi Y. (2016) The intrinsically disordered protein Atg13 mediates supramolecular assembly of autophagy initiation complexes
    Dev. Cell, DOI: 10.1016/j.devcel.2016.06.015

2015年


  • Yamamoto H.*, Shima T., Yamaguchi M., Mochizuki Y., Hoshida H., Kakuta S., Kondo-Kakuta C., Noda N.N., Itoh T., Inagaki F., Akada R., Ohsumi Y.* (2015) The thermotolerant yeast Kluyveromyces marxianus is a useful organism for structural and biochemical studies of autophagy
    J. Biol. Chem., DOI: 10.1074/jbc.M115.684233
  • Suzuki S.W., Yamamoto H.*, Oikawa Y., Kondo-Kakuta C., Kimura Y., Hirano H., Ohsumi Y.* (2015) Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation
    Proc. Natl. Acad. Sci., DOI: 10.1073/pnas.1421092112

2014年


  • Fujioka Y.*, Suzuki S.W.*, Yamamoto H.*, Kondo-Kakuta C., Kimura Y., Hirano H., Akada R., Inagaki F., Ohsumi Y., Noda N.N. (2014) Structural basis of starvation-induced assembly of the autophagy initiation complex
    Nat. Struct. Mol. Biol., DOI: 10.1038/nsmb.2822
  • Fujimoto T., Yamamoto H., Ohsumi Y. (2014) Different phosphatidylinositol 3-phosphate asymmetries in yeast and mammalian autophagosomes revealed by a new electron microscopic technique
    Autophagy, DOI: 10.4161/auto.28489
  • Cheng J., Fujita A., Yamamoto H., Tatematsu T., Kakuta S., Obara K., Ohsumi Y., Fujimoto T. (2014) Yeast and mammalian autophagosomes exhibit distinct phosphatidylinositol 3-phosphate asymmetries
    Nat. Commun., DOI: 10.1038/ncomms4207

2013年


  • Suzuki K., Akioka M., Kondo-Kakuta C., Yamamoto H., Ohsumi Y. (2013) Fine mapping of autophagy-related proteins during autophagosome formation in Saccharomyces cerevisiae
    J. Cell Sci., DOI: 10.1242/jcs.122960

2012年


  • Kakuta S., Yamamoto H., Negishi L., Kondo-Kakuta C., Hayashi N., Ohsumi Y. (2012) Atg9 vesicles recruit vesicle-tethering proteins Trs85 and Ypt1 to the autophagosome formation site
    J. Biol. Chem., DOI: 10.1074/jbc.M112.411454
  • Yamaguchi M., Matoba K., Sawada R., Fujioka Y., Nakatogawa H., Yamamoto H., Kobashigawa Y., Hoshida H., Akada R., Ohsumi Y., Noda N.N., Inagaki F. (2012) Noncanonical recognition and UBL loading of distinct E2s by autophagy-essential Atg7
    Nat. Struct. Mol. Biol., DOI: 10.1038/nsmb.2451
  • Watanabe Y., Kobayashi T., Yamamoto H., Hoshida H., Akada R., Inagaki F., Ohsumi Y., Noda N.N. (2012) Structure-based analyses reveal distinct binding sites for Atg2 and phosphoinositides in Atg18
    J. Biol. Chem., DOI: 10.1074/jbc.M112.397570
  • Nakatogawa H., Ohbayashi S., Sakoh-Nakatogawa M., Kakuta S., Suzuki S.W., Kirisako H., Kondo-Kakuta C., Noda N.N., Yamamoto H., Ohsumi Y. (2012) The autophagy-related protein kinase Atg1 interacts with the ubiquitin-like protein Atg8 via the Atg8 family interacting motif to facilitate autophagosome formation
    J. Biol. Chem., DOI: 10.1074/jbc.C112.387514
  • Yamaguchi M., Noda N.N., Yamamoto H., Shima T., Kumeta H., Kobashigawa Y., Akada R., Ohsumi Y., Inagaki F. (2012) Structural insights into Atg10-mediated formation of the autophagy-essential Atg12-Atg5 conjugate
    Structure, DOI: 10.1016/j.str.2012.04.018
  • Yamamoto H., Kakuta S., Watanabe T.M., Kitamura A., Sekito T., Kondo-Kakuta C., Ichikawa R., Kinjo M., Ohsumi Y. (2012) Atg9 vesicles are an important membrane source during early steps of autophagosome formation
    J. Cell Biol., DOI: 10.1083/jcb.201202061

2011年以前の代表的な論文


  • Yamamoto H.*, Itoh N.*, Kawano S., Yatsukawa Y., Momose T., Makio M., Matsunaga M., Yokota M., Esaki M., Shodai T., Kohda D., Hobbs A.E., Jensen R.E., Endo T. (2011) Dual role of the receptor Tom20 in specificity and efficiency of protein import into mitochondria
    Proc. Natl. Acad. Sci., DOI: 10.1073/pnas.1014918108
  • Yamamoto H., Fukui K., Takahashi H., Kitamura S., Shiota T., Terao K., Uchida M., Esaki M., Nishikawa S., Yoshihisa T., Yamano K., Endo T. (2009) Roles of Tom70 in import of presequence-containing mitochondrial proteins
    J. Biol. Chem., DOI: 10.1074/jbc.M109.041756
  • Yamamoto H., Momose T., Yatsukawa Y., Ohshima C., Ishikawa D., Sato T., Tamura Y., Ohwa Y., Endo T. (2005) Identification of a novel member of yeast mitochondrial Hsp70-associated motor and chaperone proteins that facilitates protein translocation across the inner membrane
    FEBS Lett., DOI: 10.1016/j.febslet.2004.12.018
  • Yamamoto H., Esaki M., Kanamori T., Tamura Y., Nishikawa S., Endo T. (2002) Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes
    Cell, DOI: 10.1016/s0092-8674(02)01053-x