Homeostasis of ether glycerophospholipids, plasmalogens, in tissues and its physiological functions
| Project/Area Number |
17K07337
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | 株式会社レオロジー機能食品研究所 (2019)
Kyushu University (2017-2018) |
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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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(37 results)
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[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.
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Journal Title
Plant Morphol.
Volume: in press
NAID
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
J. Cell Sci.
Volume: 133
Issue: 9
Pages: 236943-236943
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Cell Rep.
Volume: 30
Issue: 5
Pages: 1417-1433
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
J. Cell Sci.
Volume: 132
Issue: 6
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
J. Neurosci.
Volume: 37
Issue: 15
Pages: 4074-4092
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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