2007 Fiscal Year Final Research Report Summary
Molecular Mechanism of Membrane Dynamics during Autophagy
| Project/Area Number |
15002012
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Institute for Basic Biology (2004-2007)
Okazaki National Research Institutes (2003) |
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Principal Investigator |
OHSUMI Yoshinori National Institute for Basic Biology, Dept. of Cell Biology, Professor (30114416)
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| Project Period (FY) |
2003 – 2007
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| Keywords | autophagy / protein degradation / vacuole / lysosome / ATG / ubiqutin-like protein / autophagosome / nutrient starvation |
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| Research Abstract |
Recently autophagy is getting a hot field in cell biology. There appeared many papers showing physiological significance of autophagy in many important aspects in mammals. However, molecular mechanism of autophagy is still remained to be uncovered. This research project aimed to understand the dynamics of membrane during autophgy at molecular level. For 4 years of the research period, we could obtain the following progress.
Total 18 Atg proteins are essential for autophagosome formation and consist five functional units. We systematically studied localization of each Atg proteins in every atg mutant and proposed hierarchy of Atg proteins for autophagosome formation. Furthermore auophagy-specific Atg protein complex (Atg17-Atg29-Atg31) was found to be basal for PAS formation for autophagosome.
Two conjugation systems are essential for autophagy. In vitro reconstitution of Atg12 conjugation and Atg8 lipidation was established using purified yeast and plant proteins. We succeeded to show Atg8-PE causes membrane tethering and hemifusion of PE-containing liposome. Also we showed that Atg12-Atg5 conjugate catalytically stimulate the Atg8 lipidation reaction like E3 enzyme.
Localization of autophagy-specific PI3-kinase was determined by Atg14 and PI3 kinase activity and its product PI3P are required for autophagosome formation.
In collaboration with Dr. Inagaki's group we succeeded to obtain crystal structures of LC3, Atg3, Atg4B, Atg4b-LC3 complex, Atg5/Atg16 complex, and Ape1.
It was shown that autophagy is essential for maintenance of amino acid levels for protein synthesis during nitrogen starvation.
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[Journal Article] Structure of ATG5.ATG16, a complex essential for autophagy.2007
Author(s)
Matsushita, M., Suzuki, N. N., Obara, K., Fujioka, Y., Ohsumi, Y., Inagaki, F.
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Journal Title
J. Biol. Chem. 282
Pages: 6763-6772
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Crystallization and preliminary crystallographic analysis of human Atg4B-LC3 complex.2007
Author(s)
Satoo, K., Suzuki, N. N., Fujioka, Y., Mizushima, N., Ohsumi, Y., Inagaki, F.
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Journal Title
Acta Crystallograph. Sect. F. Struct. Biol. Cryst. Commun. 63
Pages: 99-102
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Crystallization of Saccharomyces cerevisiae aminopeptidase 1, the major cargo protein of the Cvt pathway.2007
Author(s)
Adachi, W., Suzuki, N. N., Fujioka, Y., Suzuki, K., Ohsumi, Y., Inagaki, F.
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Journal Title
Acta Crystallograph. Sect. F. Struct. Biol. Cryst. Commun. 63
Pages: 200-203
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The crystal structure of ATG3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates ATG8 lipidation.2007
Author(s)
Yamada, Y., Suzuki, N. N., Hanada, T., Ichimura, Y., Kumeta, H., Fujioka, Y., Ohsumi, Y., Inagaki, F.
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Journal Title
J. Biol. Chem. 282
Pages: 8036-8043
Description
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[Journal Article] Expression, purification and crystallization of the Atg5-Atg16 complex essential for autophagy.2006
Author(s)
Matsushita, M., Suzuki, N. N., Fujioka, Y., Ohsumi, Y., Inagaki, F.
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Journal Title
Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 62
Pages: 1021-1023
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Crystallization and preliminary X-ray analysis of Atg3.2006
Author(s)
Yamada, Y., Suzuki, N. N., Fujioka. Y., Ichimura, Y., Ohsumi, Y., Inagaki, F.
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Journal Title
Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 62
Pages: 1016-1017
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] AtATG genes, homologs of yeast autophagy genes, are involved in constitutive autophagy in Arabidopsis root tip cells.2006
Author(s)
Inoue, Y., Suzuki, T., Hattori, M., Yoshimoto, K., Ohsumi, Y., Moriyasu, Y.
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Journal Title
Plant Cell Physiol. 47
Pages: 1641-1652
Description
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[Journal Article] Autophagy in development and stress responses of plants.2006
Author(s)
Bassham, D. C., Laporte, M., Marty, F., Moriyasu, Y., Ohsumi, Y., Olsen, L. J., Yoshimoto, K.
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Journal Title
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[Journal Article] A sorting nexin PpAtg24 regulates vacuolar membrane dynamics during pexophagy via binding to phosphatidylinositol-3-phosphate.2005
Author(s)
Ano, Y., Hattori, T., Oku, M., Mukaiyama, H., Baba, M., Ohsumi, Y., Kato, N., Sakai, Y.
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Journal Title
Mol. Biol. Cell 16
Pages: 446-457
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy.2005
Author(s)
Kabeya, Y., Kamada, Y., Baba, M., Takikawa, H., Sasaki, M., Ohsumi, Y.
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Journal Title
Mol. Biol. Cell 16
Pages: 2544-2553
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice.2005
Author(s)
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., Kominami, E., Tanaka, K., Chiba, T.
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Journal Title
J. Cell Biol. 169
Pages: 425-434
Description
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[Journal Article] Essential roles of Atg5 and FADD in autophagic cell death : dissection of autophagic cell death into vacuole formation and cell death.2005
Author(s)
Pyo, J. O., Jang, M. H., Kwon, Y. K., Lee, H. J., Jun, J. I., Woo, H. N., Cho, D. H., Choi, B., Lee, H., Kim, J. H., Mizushima, N., Ohsumi, Y., Jung, Y. K.
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Journal Title
J. Biol. Chem. 280
Pages: 20722-20729
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization.2005
Author(s)
Kamada, Y., Fujioka, Y., Suzuki, N. N., Inagaki, F., Wullschleger, S., Loewith, R., Hall, M. N., Ohsumi, Y.
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Journal Title
Mol. Cell Biol. 25
Pages: 7239-7248
Description
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[Journal Article] Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy.2005
Author(s)
Sugawara, K., Suzuki, N. N., Fujioka, Y., Mizushima, N., Ohsumi, Y., Inagaki, F.
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Journal Title
J. Biol. Chem. 280
Pages: 40058-40065
Description
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[Journal Article] Characterization of a novel autophagy-specific gene, ATG29.2005
Author(s)
Kawamata, T., Kamada, Y., Suzuki, K., Kuboshima, N., Akimatsu, H., Ota, S., Ohsumi, M., Ohsumi, Y.
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Journal Title
Biochem. Biophys. Res. Commun. 338
Pages: 1884-1889
Description
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[Journal Article] Modification of a ubiquitin-like protein Paz2 conducted micropexophagy through formation of a novel membrane structure.2004
Author(s)
Mukaiyama, H., Baba, M., Osumi, M., Aoyagi, S., Kato, N., Ohsumi, Y., Sakai, Y.
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Journal Title
Mol. Biol. Cell 15
Pages: 58-70
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] LC3, GABARAP and GATE16 localize to autophagosomeal membrane depending on form-II formation2004
Author(s)
Kabeya, Y., Mizushima, N., Yamamoto, A., Oshitani-Okamoto, S., Ohsumi, Y., Yoshimori, T.
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Journal Title
J. Cell Sci. 117
Pages: 2805-2812
Description
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[Journal Article] The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8.2004
Author(s)
Sugawara, K., Suzuki, N. N., Fujioka, Y., Mizushuma, N., Ohsumi, Y., Inagaki, F.
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Journal Title
Genes Cells 9
Pages: 611-618
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy.2004
Author(s)
Ichimura, Y., Imamura, Y., Emoto, T., Umeda, M., Noda, T., Ohsumi, Y.
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Journal Title
J. Biol. Chem. 279
Pages: 40584-40592
Description
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[Journal Article] Processing of ATG8s, ubiquitin-like proteins, and their deconjugation by ATG4s are essential for plant autophagy.2004
Author(s)
Yoshimoto, K., Hanaoka, H., Sato, S., Kato, T., Tabata, S., Noda, T., Ohsumi, Y.
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Journal Title
Plant Cell 16
Pages: 2967-2983
Description
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[Journal Article] The role of autophagy during the early neonatal starvation period.2004
Author(s)
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., Mizushima, N.
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Journal Title
Nature 432
Pages: 1032-1036
Description
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[Journal Article] Mouse Apg16L, a novel WD-repeat protein, targets to the sutophagic isolation membrane with the Apg12-Apg5 conjugate.2003
Author(s)
Mizushima, N., Kuma, A., Kobayashi, Y., Yamamoto, A., Matsubae, M., Takao, T., Natsume, T., Ohsumi, Y., Yoshimori, T.
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Journal Title
J. Cell Sci. 116
Pages: 1679-1688
Description
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[Journal Article] A unified nomenclature for yeast autophagy-related genes.2003
Author(s)
Klionsky, D. J., Cregg, J. M., Dunn, W. A. Jr, Emr, S. D., Sakai, Y., Sandoval, I. V., Sibirny, A, Subramani, S., Thumm, M., Veenhuis, M., Ohsumi, Y.
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Journal Title
Dev. Cell 5
Pages: 539-545
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.2003
Author(s)
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E. L., Mizushima, N., Ohsumi, Y., Cattoretti, G., Levine, B.
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Journal Title
J. Clin. Invest. 112
Pages: 1809-1820
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Crystalization and preliminary X-ray analyses of LC3-I.2003
Author(s)
Sugawara, K., Suzuki, N. N., Fujioka, Y., Mizushima, N., Ohsumi, Y., Inagaki, F.
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Journal Title
Acta Crys. D. 59
Pages: 1464-1465
Description
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