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Homeostasis of ether glycerophospholipids, plasmalogens, in tissues and its physiological functions

Research Project

Project/Area Number 17K07337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research Institution株式会社レオロジー機能食品研究所 (2019)
Kyushu University (2017-2018)

Principal Investigator

Honsho Masanori  株式会社レオロジー機能食品研究所, 未登録, 研究員(移行) (90372747)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsプラスマローゲン / 脂質恒常性 / 脳 / コレステロール / ペルオキシソーム / 小脳 / 肝臓
Outline of Final Research Achievements

Synthesis of ethanolamine plasmalogen (PlsEtn) is regulated by modulating the stability of fatty acyl-CoA reductase 1 (Far1), a rate-limiting enzyme in plasmalogen synthesis. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis in cultured cells by altering the stability of squalene monooxygenase (SM). In the present study, I found that the protein but not the transcription level of Far1 in several tissues including cerebellum of the mutant mice deficient in plasmalogen synthesis was higher than that from wild-type mouse, suggesting that Far1 is stabilized by the lowered level of PlsEtn. The protein level of SM was increased, whereas the transcriptional activity of the liver X receptor (LXR), ligand-activated transcription factor, was lowered in the cerebellum of the mutant mice. These results suggest that the reduction of plasmalogens in the cerebellum compromises the cholesterol homeostasis, thereby reducing the transcriptional activities of LXR.

Academic Significance and Societal Importance of the Research Achievements

ほ乳類のプラスマローゲンは生合成のみによって供給される。さまざまな組織におけるプラスマローゲンの生合成制御機構を明らかにした本研究は、個体のプラスマローゲンの恒常性の理解に大きく貢献する成果である。
また、プラスマローゲン合成障害マウスにおけるミエリン形成異常の障害機構の解明は、プラスマローゲンが制御するコレステロール生合成調節機構の生理的重要性を明らかにしたものである。
本研究成果は、プラスマローゲンの減少が報告されているアルツハイマー病や自閉症などの脳機能障害の原因の解明、機能回復手段の開発の基礎となる社会的にも意義の高い研究成果である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (5 results) Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 12 results) Presentation (12 results) (of which Invited: 1 results) Book (5 results) Remarks (1 results)

  • [Int'l Joint Research] Columbia大学/Stanford大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Wien医科大学(オーストリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Heidelberg大学(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ハイデルベルグ大学(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] ウィーン医科大学(オーストリア)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Molecular basis of local energy generation during mitochondrial and peroxisomal division2020

    • Author(s)
      Imoto, Y. Abe, Y., Honsho, M., Okumoto, K., Ohnuma, M., Kuroiwa, H., Kuroiwa, T., and Fujiki, Y.
    • Journal Title

      Plant Morphol.

      Volume: in press

    • NAID

      130008006485

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent insights into peroxisome biogenesis and associated diseases2020

    • Author(s)
      *Fujiki, Y., Abe, Y., Imoto, Y., Tanaka, A.J., Okumoto, K., Honsho, M., Tamura, S., Miyata, N., Yamashita, T., Chung, W.K., and Kuroiwa, T.
    • Journal Title

      J. Cell Sci.

      Volume: 133 Issue: 9 Pages: 236943-236943

    • DOI

      10.1242/jcs.236943

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A peroxisome deficiency-induced reductive cytosol state up-regulates the brain-derived neurotrophic factor pathway2020

    • Author(s)
      Abe Yuichi、Honsho Masanori、Kawaguchi Ryoko、Matsuzaki Takashi、Ichiki Yayoi、Fujitani Masashi、Fujiwara Kazushirou、Hirokane Masaaki、Oku Masahide、Sakai Yasuyoshi、Yamashita Toshihide、Fujiki Yukio
    • Journal Title

      Journal of Biological Chemistry

      Volume: - Issue: 16 Pages: 5321-5334

    • DOI

      10.1074/jbc.ra119.011989

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systematic identification of regulators of oxidative stress reveals non-canonical roles for peroxisomal import and the pentose phosphate pathway.2020

    • Author(s)
      Dubreuil, M.M., Morgens, D.W., Okumoto, K., Honsho, M., Contrepois, K., Lee-McMullen, B., Traber, G.M., Sood, R.S., Dixon, S.J., Snyder, M.P., *Fujiki, Y., and *Bassik, M.C.
    • Journal Title

      Cell Rep.

      Volume: 30 Issue: 5 Pages: 1417-1433

    • DOI

      10.1016/j.celrep.2020.01.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmalogen mediates integration of adherens junction2019

    • Author(s)
      Takahashi Takanori、Honsho Masanori、Abe Yuichi、Fujiki Yukio
    • Journal Title

      The Journal of Biochemistry

      Volume: 166 Issue: 5 Pages: 423-432

    • DOI

      10.1093/jb/mvz049

    • NAID

      40022069621

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired plasmalogen synthesis dysregulates liver X receptor-dependent transcription in cerebellum2019

    • Author(s)
      Honsho Masanori、Dorninger Fabian、Abe Yuichi、Setoyama Daiki、Ohgi Ryohei、Uchiumi Takeshi、Kang Dongchon、Berger Johannes、Fujiki Yukio
    • Journal Title

      The Journal of Biochemistry

      Volume: 166 Issue: 4 Pages: 353-361

    • DOI

      10.1093/jb/mvz043

    • NAID

      40022023663

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An alternative membrane topology permits lipid droplet localization of peroxisomal fatty acyl-CoA reductase 12019

    • Author(s)
      Exner, T., Romero-Brey, I., Yifrach, E., Rivera-Monroy, J., Schrul, B., Zouboulis, C.C., Stremmel, W., Honsho, M., Bartenschlager, R., Zalckvar, E., Poppelreuther, M., and Fullekrug, J.
    • Journal Title

      J. Cell Sci.

      Volume: 132 Issue: 6

    • DOI

      10.1242/jcs.223016

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Homeostasis of plasmalogens in mammals2019

    • Author(s)
      Honsho Masanori、Fujiki Yukio
    • Journal Title

      In Encyclopedia of Food Chemistry

      Volume: 2 Pages: 218-223

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特集 細胞高次機能をつかさどるオルガネラコミュニケーション Ⅳ.ペルオキシソーム オルガネラ間の協奏によるペルオキシソームの機能と恒常性の制御2018

    • Author(s)
      藤木幸夫, 奥本寛治, 本庄雅則
    • Journal Title

      生体の科学

      Volume: 69 Issue: 6 Pages: 591-595

    • DOI

      10.11477/mf.2425200929

    • ISSN
      0370-9531, 1883-5503
    • Year and Date
      2018-12-15
    • Related Report
      2018 Research-status Report
  • [Journal Article] Regulation of peroxisome homeostasis and functions2018

    • Author(s)
      本庄 雅則、藤木 幸夫
    • Journal Title

      生化学

      Volume: 90 Issue: 1 Pages: 5-13

    • DOI

      10.14952/SEIKAGAKU.2018.900005

    • ISSN
      0037-1017
    • Year and Date
      2018-02-25
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum2018

    • Author(s)
      Abe Yuichi、Honsho Masanori、Itoh Ryota、Kawaguchi Ryoko、Fujitani Masashi、Fujiwara Kazushirou、Hirokane Masaaki、Matsuzaki Takashi、Nakayama Keiko、Ohgi Ryohei、Marutani Toshihiro、Nakayama Keiichi I、Yamashita Toshihide、Fujiki Yukio
    • Journal Title

      Life Science Alliance

      Volume: 1 Issue: 6 Pages: 1-17

    • DOI

      10.26508/lsa.201800062

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Onsite GTP fuelling via DYNAMO1 drives division of mitochondria and peroxisomes2018

    • Author(s)
      Imoto Yuuta、Abe Yuichi、Honsho Masanori、Okumoto Kanji、Ohnuma Mio、Kuroiwa Haruko、Kuroiwa Tsuneyoshi、Fujiki Yukio
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41467-018-07009-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduction of ether-type glycerophospholipids, plasmalogens, by NF-κB signal leading to microglial activation2017

    • Author(s)
      Hossain, Md. S., Abe, Y., Ali, F., Youssef, M., Honsho, M., Fujiki, Y., and *Katafuchi, T.
    • Journal Title

      J. Neurosci.

      Volume: 37 Issue: 15 Pages: 4074-4092

    • DOI

      10.1523/jneurosci.3941-15.2017

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmalogen homeostasis - regulation of plasmalogen biosynthesis and its physiological consequence in mammals2017

    • Author(s)
      Honsho Masanori、Fujiki Yukio
    • Journal Title

      FEBS Letters

      Volume: 591 Issue: 18 Pages: 2720-2729

    • DOI

      10.1002/1873-3468.12743

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 個体におけるエーテル型リン脂質プラスマローゲンの生合成制御2019

    • Author(s)
      本庄 雅則, 阿部 雄一, Dorninger Fabian, Berger Johannes, 藤木 幸夫
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ペルオキシソーム形成異常による小脳形態形成障害の病態発症機構2019

    • Author(s)
      阿部 雄一, 本庄 雅則, 伊藤 竜太, 藤谷 昌司, 中山 啓子, 大城 遼平, 中山 敬一, 山下 俊英, 藤木 幸夫
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] プラスマローゲン生合成を担うacyl/alkyl dihydroxyacetonephosphate reductaseの異なる細胞小器官への標的化とその生理的意義2019

    • Author(s)
      本庄 雅則, 田中 恵美, Raphael A. Zoeller, 藤木 幸夫
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] エーテルリン脂質プラスマローゲン依存的な上皮細胞の接着結合形成2019

    • Author(s)
      本庄 雅則, 高橋 公紀, 阿部雄一, 藤木 幸夫
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ペルオキシソーム欠損性アストロサイトにおける代謝障害とBDNF異常発現2019

    • Author(s)
      阿部 雄一, 本庄 雅則, 藤木 幸夫
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Pex14欠損マウスにおける小脳形態異常の分子機構2018

    • Author(s)
      阿部雄一、本庄雅則、藤木幸夫
    • Organizer
      平成30年度日本生化学会九州支部例会
    • Related Report
      2018 Research-status Report
  • [Presentation] Plasmalogen homeostasis links to cholesterol biosynthesis in brain2018

    • Author(s)
      Masanori Honsho、Yukio Fujiki
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ペルオキシソーム局在性テイルアンカー型膜タンパク質の輸送局在化機構2018

    • Author(s)
      奥本 寛治、 田村 茂彦、八木田 悠一、 本庄 雅則、 藤木 幸夫
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] プラスマローゲン生合成機構:acyl/alkyl dihydroxyacetonephosphate還元酵素(DHRS7B)のペルオキシソームと小胞体への標的化機構2017

    • Author(s)
      田中恵美、 本庄雅則、 藤木幸夫
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] エーテルリン脂質プラスマローゲンの生合成を制御するセンシング機構2017

    • Author(s)
      本庄雅則、 阿部雄一、 藤木幸夫
    • Organizer
      第59回日本脂質生化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] エーテルリン脂質プラスマローゲンの恒常性維持機構とその生理的意義2017

    • Author(s)
      本庄 雅則、藤木 幸夫
    • Organizer
      2017年度 生命科学系学会合同年次大会ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] PEX14障害マウスにおける小脳形態異常2017

    • Author(s)
      阿部 雄一、本庄 雅則、大城 遼平、藤木 幸夫
    • Organizer
      2017年度 生命科学系学会合同年次大会ConBio2017
    • Related Report
      2017 Research-status Report
  • [Book] Peroxisome: metabolic functions and biogenesis. In: Lizard, G. (ed.) Peroxisomes in Neurodegenerative Diseases2020

    • Author(s)
      Okumoto, K., Tamura, S., Honsho, M., and Fujiki, Y.
    • Publisher
      Springer Nature
    • Related Report
      2019 Annual Research Report
  • [Book] Peroxisome biogenesis disorders. In: Lizard, G. (ed.) Peroxisomes in Neurodegenerative Diseases2020

    • Author(s)
      Honsho, M., Okumoto, K., Tamura, S., and *Fujiki, Y.
    • Publisher
      Springer Nature
    • Related Report
      2019 Annual Research Report
  • [Book] A mouse model system to study peroxisomal roles in neurodegeneration of peroxisome biogenesis disorders. In: Lizard, G. (ed.) Peroxisomes in Neurodegenerative Diseases2020

    • Author(s)
      Abe, Y., Tamura, S., Honsho, M., and Fujiki, Y.
    • Publisher
      Springer Nature
    • Related Report
      2019 Annual Research Report
  • [Book] 医学のあゆみ 特集「脂質クオリティ研究の基礎と臨床」 プラスマローゲン恒常性とその障害による疾患2019

    • Author(s)
      本庄 雅則、藤木 幸夫
    • Total Pages
      5
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2019 Annual Research Report
  • [Book] 実験医学 第35巻11号 「ペキソファジー:ペルオキシソームの形成・機能制御と分解機構」2017

    • Author(s)
      藤木幸夫, 山下俊一, 奥本寛治, 本庄雅則
    • Total Pages
      8
    • Publisher
      羊土社
    • Related Report
      2017 Research-status Report
  • [Remarks] 生体防御医学研究所 オルガネラホメオスタシス研究室

    • URL

      http://www.organelle.kyushu-u.ac.jp/lab/organellestasis/index.html

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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