Peroxisome biogenesis and human disorders
Project/Area Number |
17H03675
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cell biology
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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) |
Principal Investigator |
Fujiki Yukio 株式会社レオロジー機能食品研究所, 未登録, 顧問研究員、九州大学-レオロジー機能食品研究所 共同研究代表 (70261237)
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Co-Investigator(Kenkyū-buntansha) |
田村 茂彦 九州大学, 基幹教育院, 教授 (90236753)
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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 |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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Keywords | ペルオキシソーム / PEX遺伝子 / カタラーゼ細胞内輸送制御 / プラスマローゲン / 神経形成障害 / 脳由来神経栄養因子(BDNF) / ノックアウトマウス / 膜形成 / オルガネラ分裂 |
Outline of Final Research Achievements |
We have investigated peroxisome biogenesis and human deficiency disorders (PBD). A number of outcomes include 1) we identified two splicing variants localized to peroxisomes of human mitochondrial Rho GTPase-1 (Miro1), both being involved in microtubule-dependent long-range movement of peroxisomes; 2) we discovered that the catalase released from peroxisomes via BAK pore eliminates H2O2, a toxic and major causative of the oxidative stress, in the cytosol for cell survival; 3) we discovered that the 17-kDa nucleoside diphosphate kinase-like protein, DYNAMO1, locally generates GTP in mitochondrial division and peroxisome-dividing machineries; 4) to uncover the pathological mechanisms underlying PBD, we established a new PBD mouse model that is defective in Pex14, termed the Pex14ΔC/ΔC mouse. The Pex14ΔC/ΔC mouse shows an impaired dendritic development of Purkinje cells in cerebellum that is caused by a dysregulation of the brain-derived neurotrophic factor (BDNF)-TrkB pathway.
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Academic Significance and Societal Importance of the Research Achievements |
細胞機能の発現は、新生タンパク質の細胞内小器官への選別輸送・局在化により実現される。その障害は、オルガネラ欠損症などの重篤な病態をもたらす。本研究では、ペルオキシソームの形成と欠損症の分子基盤解明に取り組んだ。代表的成果として、ペルオキシソームの細胞内移動を担うMiro1分子の発見、酸化ストレス時のカタラーゼによる細胞死防御戦略の発見、ペルオキシソームやミトコンドリアの分裂に必須なGTP供給因子Dynamo1の発見、世界で初めてのペルオキシソーム欠損症の小脳形成障害機構の解明等がある。多くの新知見は他のオルガネラの生体内恒常性維持機構とその破綻の解明研究にも大きな波及効果を有する。
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Report
(4 results)
Research Products
(93 results)
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[Journal Article] Peroxisome counteracts oxidative stresses by suppressing catalase import via phosphorylation of Pex14 in the import machinery.2020
Author(s)
Okumoto, K., El Shermely, M., Natsui, M., Kosako, H., Natsuyama, R., Marutani, T., and *Fujiki, Y. (*: corresponding author)
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Journal Title
bioRxiv (eLife, in revision)
Volume: -
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mitotic phosphorylation of Pex14p regulates peroxisomal import machinery in mammals.2020
Author(s)
Yamashita, K., Tamura, S., Honsho, M., Yada, H., Yagita, Y., Kosako, H., and *Fujiki, Y.
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Journal Title
J. Cell Biol.
Volume: in press
Related Report
Peer Reviewed / Open Access
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[Journal Article] Molecular basis of local energy generation during mitochondrial and peroxisomal division.2020
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] Dynamics of the nucleoside diphosphate kinase protein DYNAMO2 correlates with the changes in the global GTP level during the cell cycle of <i>Cyanidioschyzon merolae</i>2019
Author(s)
Imoto, Y., Abe, Y., Okumoto, K., Ohnuma, M., Kuroiwa, H., Kuroiwa, T., and Fujiki, Y.
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Journal Title
Proceedings of the Japan Academy, Series B
Volume: 95
Issue: 2
Pages: 75-85
DOI
NAID
ISSN
0386-2208, 1349-2896
Year and Date
2019-02-08
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent pathway of apoptosis.2019
Author(s)
Tanaka, H., *Okazaki, T., Aoyama, S., Yokota, M., Koike, M., Okada, Y., Fujiki, Y., and Gotoh, Y.
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Journal Title
J. Cell Sci.
Volume: -
Issue: 11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A newly identified mutation in the PEX26 gene is associated with a milder form of Zellweger spectrum disorder.2019
Author(s)
Tanaka, A. J., Okumoto, K., Tamura, S., Abe, Y., Hirsch, Y., Deng, L., Ekstein, J., Chung, W. K., and Fujiki Y.
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Journal Title
Cold Spring Harb. Mol. Case Stud.
Volume: 5
Issue: 1
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A newly isolated Pex7-binding, atypical PTS2 protein P7BP2 is a novel dynein-type AAA+ protein.2018
Author(s)
Niwa, H., Miyauchi-Nanri, Y., Okumoto, K., Mukai, S., Noi, K., Ogura, T., and Fujiki Y.
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Journal Title
J. Biochem.
Volume: 164
Pages: 437-447
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] New splicing variants of mitochondrial Rho GTPase-1 (Miro1) transport peroxisomes.2018
Author(s)
Okumoto, K., Ono, T., Toyama, R., Shimomura, A., Nagata, A., and Fujiki Y.
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Journal Title
J. Cell Biol.
Volume: 217
Issue: 2
Pages: 619-633
DOI
Related Report
Peer Reviewed / Open Access
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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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[Presentation] Peroxisome homeostasis and biogenesis disorders2019
Author(s)
Fujiki, Y., Hosoi, K., Miyata, N., Mukai, S., Okumoto, K., Cheng, E.H., Abe, Y., Honsho, M., Itoh, R., Nakayama, K., Nakayama, K.-I., and Yamashita, T.
Organizer
NME 2019: 11th international congress of the NME/NDPK.NM23/AWD Gene Family
Related Report
Int'l Joint Research
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[Presentation] Pathological mechanism of peroxisome biogenesis disorders2019
Author(s)
Yuichi Abe, Masanori Honsho, Ryota Itoh, Ryoko Kawaguchi, Masashi Fujitani, Kazushirou Fujiwara, Masaaki Hirokane, Takashi Matsuzaki, Keiko Nakayama, Ryohei Ohgi, Toshihiro Marutani, Keiichi I. Nakayama, Toshihide Yamashita, and Yukio Fujiki
Organizer
EMBO Workshop “Current advances in protein translocation across membranes”
Related Report
Int'l Joint Research
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