The role of autophagy in adipocyte-differentiation and lipid metabolism

• Project/Area Number: 19390079
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Juntendo University
• Principal Investigator: KOMINAMI Eiki Juntendo University, 医学部, 教授 (10035496)
• Co-Investigator(Kenkyū-buntansha): NORIHIKO Furuya 順天堂大学, 医学部, 助教 (50401188) ; EZAKI Junji 順天堂大学, 医学部, 准教授 (60232948)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: オートファジー / 脂肪滴(Lipid droplet) / 脂肪細胞 / 細胞分化 / ノックアウトマウス / Lipid droplet / 脂質代謝 / Atg7 / トリアシルグリセロール

Research Abstract

細胞質成分の大規模分解系であるオートファジーと脂質代謝および脂肪細胞の分化との関わりを明らかにする目的で、脂肪組織特異的オートファジー不能マウスおよびオートファジー不能細胞を脂肪細胞へと分化させ解析した。その結果、オートファジーは細胞内の中性脂肪を蓄積するオルガネラである脂肪滴の形成機構には関わらないが、前駆細胞から脂肪細胞への分化に転写レベルで関わっていることが認められた。

Research Products

• [Journal Article] Characterization of CAA0225, anovel inhibitor specific for cathepsin L, as a probe for autophagic proteolysis (2009)
  • Author(s): Takahashi K, Ueno T, Tanida I, Minematsu-Ikeguchi N, Murata M, Kominami E
  • Journal Title: Biol Pharm Bull 32(3) Pages: 475-9
  • Peer Reviewed
• [Journal Article] Participation of autophagy in the initiation of graft dysfunction after ratliver transplantation (2009)
  • Author(s): Gotoh K, Lu Z, Morita M, Shibata M, Koike M, Waguri S, Dono K, Doki Y, Kominami E, Sugioka A, Monden M, Uchiyama Y
  • Journal Title: Autophagy 5(3) Pages: 351-60
  • Peer Reviewed
• [Journal Article] The MAP1-LC3 conjugation systemis involved in lipid droplet formation (2009)
  • Author(s): Shibata M, Yoshimura K, Furuya N, Koike M, Ueno T, Komatsu M, Arai H, Tanaka K, Kominami E, Uchiyama Y
  • Journal Title: Biochem Biophys Res Commun 382(2) Pages: 419-23
  • Peer Reviewed
• [Journal Article] The MAP1-LC3 conjugation system is involved in lipid droplet formation (2009)
  • Author(s): Shibata M., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 382(2) Pages: 419-423
  • Peer Reviewed
• [Journal Article] Consideration about negativecontrols for LC3 and expression vectors for four colored fluorescent protein-LC3 negative controls (2008)
  • Author(s): Tanida I, Yamaji T, Ueno T, Ishiura S, Kominami E, Hanada K
  • Journal Title: Autophagy 4(1) Pages: 131-4
  • Peer Reviewed
• [Journal Article] Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury (2008)
  • Author(s): Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, WaguriS, Kawahara N, Kuida K, Nagata S, Kominami E, Tanaka K, Uchiyama Y
  • Journal Title: Am J Pathol 172(2) Pages: 454-69
  • Peer Reviewed
• [Journal Article] Comprehensive proteomicsanalysis of autophagy-deficient mouseliver (2008)
  • Author(s): Matsumoto N, Ezaki J, Komatsu M, Takahashi K, Mineki R, Taka H, Kikkawa M, Fujimura T, Takeda-Ezaki M, Ueno T, Tanaka K, Kominami E
  • Journal Title: Biochem Biophys Res Commun 368(3) Pages: 643-9
  • Peer Reviewed
• [Journal Article] Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation (2008)
  • Author(s): Ueno T, Sato W, Horie Y, Komatsu M, Tanida I,Yoshida M, Ohshima S, Mak TW, Watanabe S, Kominami E
  • Journal Title: Autophagy 4(5) Pages: 692-700
  • Peer Reviewed
• [Journal Article] Structural basis for sorting mechanism of p62 in selective autophagy (2008)
  • Author(s): Ichimura Y, Kumanomidou T, Sou YS, Mizushima T, Ezaki J, Ueno T, Kominami E,Yamane T, Tanaka K, Komatsu M
  • Journal Title: J Biol Chem 283(33) Pages: 22847-57
  • Peer Reviewed
• [Journal Article] Hepatic gap junctions in thehepatocarcinogen-resistant DRH rat (2008)
  • Author(s): Gotow T, Shiozaki M, Higashi T, Yoshimura K, Shibata M, Kominami E, Uchiyama Y
  • Journal Title: Histochem Cell Biol 130(3) Pages: 583-94
  • Peer Reviewed
• [Journal Article] Autophagy is important in islethomeostasis and compensatory increase ofbeta cell mass in response to high-fat diet (2008)
  • Author(s): Ebato C, Uchida T, Arakawa M, Komatsu M,Ueno T, Komiya K, Azuma K, Hirose T, Tanaka K, Kominami E, Kawamori R, Fujitani Y,Watada H
  • Journal Title: Cell Metab 8(4) Pages: 325-32
  • Peer Reviewed
• [Journal Article] Selective turnover of p62/A170/SQSTM1 by autophagy. Ichimura Y (2008)
  • Author(s): Kominami E, Tanaka K, Komatsu M
  • Journal Title: Autophagy 4(8) Pages: 1063-6
  • Peer Reviewed
• [Journal Article] The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice (2008)
  • Author(s): Sou YS, Waguri S, Iwata J, Ueno T, Fujimura T, Hara T, Sawada N, Yamada A, Mizushima N, Uchiyama Y, Kominami E, Tanaka K, Komatsu M
  • Journal Title: Mol Biol Cell 19(11) Pages: 4762-75
  • Peer Reviewed
• [Journal Article] Differentiation-specific expression and localization of an autophagosomal marker protein (LC3) in human epidermal keratinocytes (2008)
  • Author(s): Haruna K, Suga Y, Muramatsu S, Taneda K, Mizuno Y, Ikeda S, Ueno T, Kominami E, Tanida I, Tanida I, Hanada K
  • Journal Title: J Dermatol Sci 52(3) Pages: 213-5
  • Peer Reviewed
• [Journal Article] Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation. (2008)
  • Author(s): Ueno T., et al.
  • Journal Title: Autophagy 4 Pages: 692-700
  • Peer Reviewed
• [Journal Article] Structural basis for sorting mechanism of p62 in selective autophagy. (2008)
  • Author(s): Ichimura Y., et al.
  • Journal Title: T. Biol. Chem. 283 Pages: 22847-22857
  • Peer Reviewed
• [Journal Article] Hepatic gap junctions in the hepatocarcinogen-resistant DRH rat. (2008)
  • Author(s): Gotow T., et al.
  • Journal Title: Histochem Cell Biol. 130 Pages: 583-594
  • Peer Reviewed
• [Journal Article] Differentiation-specific expression and localization of an autophagosomal marker protein (LC3)in human epidermal keratinocytes. (2008)
  • Author(s): Haruna K., et al.
  • Journal Title: J. Dermato1. Sci. 52 Pages: 213-215
  • Peer Reviewed
• [Journal Article] The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. (2008)
  • Author(s): Sou YS., et al.
  • Journal Title: Mol. Biol. Cell 19 Pages: 4762-4775
  • Peer Reviewed
• [Journal Article] Selective turnover of P62/A170/SQSTMl by autophagy. (2008)
  • Author(s): Ichimura Y., et al.
  • Journal Title: Autophagy 4 Pages: 1063-1066
  • Peer Reviewed
• [Journal Article] Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. (2008)
  • Author(s): Ebato C., et al.
  • Journal Title: Cell Metab. 8 Pages: 325-332
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes (2008)
  • Author(s): Klionsky DJ., et. al.
  • Journal Title: Autophagy 4 Pages: 151-175
  • Peer Reviewed
• [Journal Article] Consideration about negative controls for LC3 and expression vectors forfour colored fluorescent protein-LC3 negative controls (2008)
  • Author(s): Tanida I., et. al.
  • Journal Title: Autophagy 4 Pages: 131-134
  • Peer Reviewed
• [Journal Article] Comprehensive proteomics analysis of autophagy-deficient mouse liver (2008)
  • Author(s): Matsumoto N., et. al.
  • Journal Title: Biochem Biophys Res Commun. 368 Pages: 643-649
  • Peer Reviewed
• [Journal Article] Inhibition of autophagy prevents hippocampal pyramidal neuron deathafter hypoxic-ischemic injury (2008)
  • Author(s): Koike M., et. al.
  • Journal Title: Am J Pathol. 172 Pages: 151-175
  • Peer Reviewed
• [Journal Article] Komatsu M, Wang QJ, Holstein GR, Friedrich VL Jr, Iwata J, Kominami E, Chait BT,Tanaka K, Yue Z (2007)
  • Author(s): Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration
  • Journal Title: Proc Natl Acad Sci USA 104(36) Pages: 14489-94
  • Peer Reviewed
• [Journal Article] Crystal structure of Ufc1, the Ufm1-conjugating enzyme (2007)
  • Author(s): Mizushima T, Tatsumi K, Ozaki Y, Kawakami T, Suzuki A,Ogasahara K, Komatsu M, Kominami E, TanakaK, Yamane T
  • Journal Title: Biochem Biophys Res Commun 362(4) Pages: 1079-84
  • Peer Reviewed
• [Journal Article] Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice (2007)
  • Author(s): Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S, Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Kobayashi A, Yamamoto M, Yue Z, Uchiyama Y, Kominami E, Tanaka K
  • Journal Title: Cell 131(6) Pages: 1149-63
  • Peer Reviewed
• [Journal Article] Homeostatic levels of p62 control cytoplasmic inclusion body formationin autophagy-deficient mice (2007)
  • Author(s): Komatsu M., et. al.
  • Journal Title: Cell 14 Pages: 1149-1163
  • Peer Reviewed
• [Journal Article] Essential role for autophagy protein Atg7 in the maintenance of axonalhomeostasis and the prevention of axonal degeneration (2007)
  • Author(s): Komatsu M., et. al.
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 14489-14494
  • Peer Reviewed
• [Journal Article] Constitutive autophagy:vital role in clearance of unfavorable proteins in neurons (2007)
  • Author(s): Komatsu M., et. al.
  • Journal Title: Cell Death Differ. 14 Pages: 887-894
  • Peer Reviewed
• [Journal Article] Phospholipase C-related inactive protein is involved in trafficking of amma2 subunit-containing GABA(A)receptors to the cell surface (2007)
  • Author(s): Mizokami A., et. al.
  • Journal Title: J Neurosci. 27 Pages: 1692-1701
  • Peer Reviewed
• [Presentation] オートファジーに必須のE1様酵素 (2008)
  • Author(s): Tanida I. et al
  • Organizer: の新規機能領域第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice (2008)
  • Author(s): Sou YS. et al
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 選択的オートファジーにおけるp62選別機構の構造基盤 (2008)
  • Author(s): Ichimura Y
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] オートファジーに必須のEl様酵素、Atg7、の新規機能領域 (2008)
  • Author(s): Tanida I., et al.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. (2008)
  • Author(s): Sou YS., Et al.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Structural basis for sorting mechanism of p62 in selective autophagy (2008)
  • Author(s): Ichimura Y
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-01
• [Presentation] Structural basis for sorting mechanism of p62 in selective autophagy. (2008)
  • Author(s): Ichimura Y., et al.
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-01
• [Presentation] Selective autophagy regulates formation of cytoplasmic inclusions (2007)
  • Author(s): Komatsu M
  • Organizer: 第30回日本分子生物学年会・第80回日本生化学回大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Autophagosome formation in the starved animal (2007)
  • Author(s): Ezaki J
  • Organizer: 第30回日本分子生物学年会・第80回日本生化学回大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] The Atg8 conjugation system is essential for completion of autophagosomal formation in mice (2007)
  • Author(s): Sou Y
  • Organizer: 第30回日本分子生物学年会・第80回日本生化学回大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Selective autophagy regulates formation of cytoplasmic inclusions (2007)
  • Author(s): Komatsu M., et. al.
  • Organizer: 第30回日本分子生物学年会・第80回目本生化学回大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] The Atg8 conjugation system is essential for completion of autophagosomal formahon m mice (2007)
  • Author(s): Sou Y., et. al.
  • Organizer: 第30回日本分子生物学年会・第80回目本生化学回大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Selective autophagy regulates formation of intracytoplasmic inclusions (2007)
  • Author(s): Komatsu M
  • Organizer: Keystone Symposium on Autophagy in Healthand Disease
  • Place of Presentation: Monterey, California, USA
  • Year and Date: 2007-04-19
• [Presentation] GABARAP-lipidation during differentiaton and Visualization of GABARAP in mice (2007)
  • Author(s): Tanida I
  • Organizer: Keystone Symposium on Autophagy in Health and Disease
  • Place of Presentation: Monterey, California, USA
  • Year and Date: 2007-04-19
• [Presentation] Autophagosome formation resoponse to nutrient starvatior (2007)
  • Author(s): Ezaki J
  • Organizer: Keystone Symposium on Autophagy in Health and Disease
  • Place of Presentation: Monterey, California, USA
  • Year and Date: 2007-04-19
• [Presentation] Selective autophagy regulates formation of intracytoplasmic inclusions (2007)
  • Author(s): Komatsu M., et. al.
  • Organizer: Keystone Symposium on Autophagy in Health andDisease
  • Place of Presentation: Monterey,California,USA
  • Year and Date: 2007-04-19
• [Presentation] GABARAP-lipidation during differentiaton and Visualization of GABARAP in mice (2007)
  • Author(s): Tanida I., et. al.
  • Organizer: Keystone Symposium on Autophagy in Health andDisease
  • Place of Presentation: Monterey,California,USA
  • Year and Date: 2007-04-19
• [Presentation] Autophagosome formation resoponse to nutrient starvatior (2007)
  • Author(s): Ezaki J., et. al.
  • Organizer: Keystone Symposium on Autophagy in Health and Disease
  • Place of Presentation: Monterey,California,USA
  • Year and Date: 2007-04-19
• [Presentation] Role of p62/SQSTMI degradation by autophagy in cytoplasmic inclusion formation (2007)
  • Author(s): Komatsu M., et. al.
  • Organizer: Gordon Research Conferemces on Autophagy in stress, Development and disease
  • Place of Presentation: Ventura,CA,USA
  • Year and Date: 2007-01-09
• [Presentation] Autophagosome formation resoponse to nutrient starvation (2007)
  • Author(s): Ezaki J., et. al.
  • Organizer: Gordon Reseazch Conferemces on Autophagy in stress, Development and disease
  • Place of Presentation: Ventura,CA,USA
  • Year and Date: 2007-01-09
• [Presentation] Roleof p62/SQSTM1 degradation by autophagy incytoplasmic inclusion formation
  • Author(s): Komatsu M
  • Organizer: Gordon Research Conferemces on Autophagy instress
  • Place of Presentation: Ventura, CA, USA
• [Presentation] Autophagosome formation resoponse to nutrientstarvation
  • Author(s): Ezaki J
  • Organizer: Gordon Research Conferemceson Autophagy in stress, Development and disease January
  • Place of Presentation: Ventura, CA, USA
• [Book] Methods Enzymol (2009)
  • Author(s): Ezaki J, Komatsu M, Yokota S, Ueno T, Kominami E
  • Publisher: Method for monitoring pexophagy in mammalian cells
• [Book] Methods in Enzymology, Chapter 14“Method for Monitoring Pexophagy in Mammalian Cell" (2009)
  • Author(s): Ezaki J., et al.
  • Publisher: Academic Press
• [Book] Methods Mol Biol (2008)
  • Author(s): Tanida I, Ueno T, Kominami E
  • Publisher: LC3 and Autophagy
• [Book] Methods in Molecular Biology, Chapter 4“Autophagosome and Phagosome" (2008)
  • Author(s): Tanida I., et al.
  • Publisher: Humana Press
• [Remarks]
  • URL: http://www.juntendo.ac.jp/graduate/1aboratory/labo/seikagaku_saibo_seigyo/gyoseki.html
• [Remarks]
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/seikagaku_saibo_seigyo/gyoseki.html