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Elucidation of molecular mechanism of autophagy and lipid metabolism supporting soundness of organelles

Research Project

Project/Area Number 16K07689
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied biochemistry
Research InstitutionKyoto University

Principal Investigator

Oku Masahide  京都大学, 農学研究科, 助教 (10511230)

Research Collaborator ABE Masato  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsオートファジー / カルジオリピン / 脂肪滴 / ペルオキシソーム / ミクロオートファジー / 液胞
Outline of Final Research Achievements

The aim of this project was to elucidate the molecular mechanism underlying maintenance of organelles functionality. In particular, the mitochondrion emitting reactive-oxygen species (ROS) and the lipid droplet, a major storage site of neutral lipids, were chosen as the objects of the studies on the lipid dynamics and autophagy system.
Through this project, the substrate specificity of a yeast enzyme termed tafazzin was revealed as a determinant of the composition of fatty acid moiety within the mitochondrial lipid, cardiolipin. As with the lipid droplet, the role of an autophagy-related protein, Atg8, was uncovered in counteracting degradation of neutral lipids through lipolysis. In addition, a new type of autophagy (microautophagy) was discovered that is dependent on the so-called ESCRT proteins.

Academic Significance and Societal Importance of the Research Achievements

本研究では、カルジオリピンがいかにして不飽和脂肪酸鎖を多く含むリン脂質として合成されるのか、という問いについて、タファジンという、ヒトの疾患にも関与する酵素の基質特異性から答えを得られたことが大きな意義である。また、脂肪滴の量調節は細胞内の中性脂質量も左右する重要性をもつが、オートファジーに機能するタンパク質がこの量調節に機能するという発見は、哺乳類細胞にも共通するもので普遍的重要性を持つと考えられる。さらに、リソソーム(液胞)膜が直接変形して分解対象を取り込むミクロオートファジーの新たな分子機構を提示することができたことは、オートファジーの多様性理解に大きく貢献したと考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017 2016 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Peroxisomal Fba2p and Tal2p complementally function in the rearrangement pathway for xylulose 5-phosphate in the methylotrophic yeast Pichia pastoris2019

    • Author(s)
      Fukuoka Hirotaka、Kawase Takato、Oku Masahide、Yurimoto Hiroya、Sakai Yasuyoshi、Hayakawa Takashi、Nakagawa Tomoyuki
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 印刷中 Issue: 1 Pages: 33-38

    • DOI

      10.1016/j.jbiosc.2019.01.008

    • NAID

      40021953981

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolution from covalent conjugation to non-covalent interaction in the ubiquitin-like ATG12 system2019

    • Author(s)
      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.
    • Journal Title

      Nat. Struct. Mol. Biol.

      Volume: 26 Issue: 4 Pages: 289-296

    • DOI

      10.1038/s41594-019-0204-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Three Distinct Types of Microautophagy Based on Membrane Dynamics and Molecular Machineries2018

    • Author(s)
      Oku Masahide、Sakai Yasuyoshi
    • Journal Title

      BioEssays

      Volume: 40 Issue: 6 Pages: 1800008-1800008

    • DOI

      10.1002/bies.201800008

    • NAID

      120006491983

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ethanol represses the expression of methanol-inducible genes via acetyl-CoA synthesis in the yeast Komagataella phaffii2018

    • Author(s)
      Ohsawa Shin、Nishida Susumu、Oku Masahide、Sakai Yasuyoshi、Yurimoto Hiroya
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 18051-18051

    • DOI

      10.1038/s41598-018-36732-2

    • NAID

      120006546165

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evidence for ESCRT- and clathrin-dependent microautophagy.2017

    • Author(s)
      Masahide Oku, Yuichiro Maeda, Yoko Kagohashi, Takeshi Kondo, Mai Yamada, Toyoshi Fujimoto, Yasuyoshi Sakai
    • Journal Title

      Journal of Cell Biology

      Volume: 216 Issue: 10 Pages: 3263-3274

    • DOI

      10.1083/jcb.201611029

    • NAID

      120006454716

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of Acyl Chain Composition of Phosphatidylcholine in Tafazzin-Mediated Remodeling of Cardiolipin in Liposomes.2017

    • Author(s)
      Abe M, Sawada Y, Uno S, Chigasaki S, Oku M, Sakai Y, Miyoshi H.
    • Journal Title

      Biochemistry

      Volume: 56 Issue: 47 Pages: 6268-6280

    • DOI

      10.1021/acs.biochem.7b00941

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autophagy-independent function of Atg8 in lipid droplet dynamics in yeast2017

    • Author(s)
      Yuichiro Maeda, Masahide Oku, Yasuyoshi Sakai
    • Journal Title

      Journal of Biochemistry

      Volume: 161 Pages: 339-348

    • DOI

      10.1093/jb/mvw078

    • NAID

      40021219801

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin2016

    • Author(s)
      Abe M, Hasegawa Y, Oku M, Sawada Y, Tanaka E, Sakai Y, Miyoshi H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 30 Pages: 15491-15502

    • DOI

      10.1074/jbc.m116.718510

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] The dynamics of lipid droplets at the crossroads between autophagy and lipolysis2018

    • Author(s)
      Masahide Oku
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ミクロオートファジーの分子機構、生理機能の多様性2018

    • Author(s)
      奥公秀、阪井康能
    • Organizer
      日本農芸化学会 2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脂肪滴量制御におけるオートファジーおよびESCRTタンパク質の機能2018

    • Author(s)
      奥公秀、阪井康能
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 酵母脂肪滴の動態解析に有用な新たなマーカータンパク質の発見2017

    • Author(s)
      奥公秀、籠橋葉子、前田佑一郎、阪井康能
    • Organizer
      酵母遺伝学フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] 酵母脂肪滴のダイナミクスに関わるオートファジー2017

    • Author(s)
      奥公秀
    • Organizer
      第8回 愛媛微生物(NAME)フォーラム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Functional involvements of Autophagy-related (Atg) proteins in lipid droplet dynamics2016

    • Author(s)
      Masahide Oku, Yuichiro Maeda, Yasuyoshi Sakai
    • Organizer
      14th International Conferense on Yeast
    • Place of Presentation
      淡路夢舞台国際会議場
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脂肪滴恒常性に寄与するAtgタンパク質の機能解明2016

    • Author(s)
      奥公秀,前田佑一郎,阪井康能
    • Organizer
      第68回日本細胞生物学会大会 Symposium S15-6
    • Place of Presentation
      京都テルサ
    • Related Report
      2016 Research-status Report
  • [Book] Methods in Molecular Biology, Peroxisomes2017

    • Author(s)
      Shun-ichi Yamashita, Masahide Oku, Yasuyoshi Sakai, Yukio Fujiki
    • Total Pages
      7
    • Publisher
      Humana Press, New York
    • ISBN
      9781493969357
    • Related Report
      2017 Research-status Report
  • [Book] Methods in Molecular Biology, Experimental Systems to Study Yeast Pexophagy2017

    • Author(s)
      Shun-ichi Yamashita, Masahide Oku, Yasuyoshi Sakai, Yukio Fujiki
    • Total Pages
      7
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都大学大学院 農学研究科 応用生命科学専攻 制御発酵学分野

    • URL

      http://www.seigyo.kais.kyoto-u.ac.jp/

    • Related Report
      2017 Research-status Report
  • [Remarks] http://www.seigyo.kais.kyoto-u.ac.jp/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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