Monitoring autophagy dynamics in vivo using innovative tools
| Project/Area Number |
18H02611
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Juntendo University (2019-2020)
Niigata University (2018) |
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Principal Investigator |
Komatsu Masaaki 順天堂大学, 医学(系)研究科(研究院), 教授 (90356254)
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| Co-Investigator(Kenkyū-buntansha) |
大江 知之 慶應義塾大学, 薬学部(芝共立), 准教授 (30624283)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | オートファジー / 選択的オートファジー / Nrf2 / LC3 / Keap1 / オートファジープローブ / 低分子化合物 / プローブ / p62 / 化合物 |
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| Outline of Final Research Achievements |
On the basis of this research project, we have succeeded for the first time in developing selective autophagy inhibitory mice. This genetic modified mouse will be a powerful tool for autophagy research, including the physiological significance of selective autophagy, and the screening of novel autophagy substrates. We have also developed a potent Nrf2 activator, KMN003, based on molecular mechanisms and confirmed its efficacy in vivo. Since Nrf2 activators are potential therapeutic agents for multiple sclerosis and diabetic nephropathy, we expect to verify their efficacy using these pathological mouse models.
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| Academic Significance and Societal Importance of the Research Achievements |
世界初の選択的オートファジー阻害マウスの開発に成功した。また、強力なNrf2活性化剤KMN003を開発し、マウス生体内においてもその効果を確かめた。オートファジー、Nrf2ともに神経変性疾患やがん等の重篤疾患の発症予防に中心的な役割を持つことが分かっており、本研究により開発されたマウスや低分子化合物が、基礎研究のみならずヒト疾患発症機構の解明や予防機序の解明に役立つことが期待される。
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response2021
Author(s)
Kageyama S, Gudmundsson SR, Sou YS, Ichimura Y, Tamura N, Kazuno S, Ueno T, Miura Y, Noshiro D, Abe M, Mizushima T, Miura N, Okuda S, Motohashi H, Lee JA, Sakimura K, Ohe T, Noda NN, Waguri S, Eskelinen EL, Komatsu M.
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 16-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Inhibitors of the protein-protein interaction between phosphorylated p62 and Keap1 attenuate chemoresistance in a human hepatocellular carcinoma cell line2020
Author(s)
Daisuke Yasuda, Tomoyuki Ohe, Kyoko Takahashi, Riyo Imamura, Hirotatsu Kojima, Takayoshi Okabe, Yoshinobu Ichimura, Masaaki Komatsu, Masayuki Yamamoto, Tetsuo Nagano, Tadahiko Mashino
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Journal Title
Free Radical Research
Volume: Mar 30
Issue: 11-12
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy2020
Author(s)
Cabrera-Serrano Macarena、Coote David Joseph、Azmanov Dimitar、Goullee Hayley、Andersen Erik、McLean Catriona、Davis Mark、Ishimura Ryosuke、Stark Zornitza、Vallat Jean-Michel、Komatsu Masaaki、Kornberg Andrew、Ryan Monique、Laing Nigel G、Ravenscroft Gina
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Journal Title
Journal of Medical Genetics
Volume: -
Issue: 12
Pages: 835-842
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Loss of autophagy impairs physiological steatosis by accumulation of NCoR1.2019
Author(s)
Takahashi SS, Sou YS, Saito T, Kuma A, Yabe T, Sugiura Y, Lee HC, Suematsu M, Yokomizo T, Koike M, Terai S, Mizushima N, Waguri S, Komatsu M.
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Journal Title
Life Sci Alliance.
Volume: 3
Issue: 1
Pages: 201900513-201900513
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] An atypical LIR motif within UBA5 (ubiquitin like modifier activating enzyme 5) interacts with GABARAP proteins and mediates membrane localization of UBA5.2019
Author(s)
Huber J, Obata M, Gruber J, Akutsu M, L?hr F, Rogova N, Guntert P, Dikic I, Kirkin V, Komatsu M, Dotsch V, Rogov VV.
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Journal Title
Autophagy
Volume: 16
Issue: 2
Pages: 256-270
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Autophagy regulates lipid metabolism through selective turnover of NCoR12019
Author(s)
Saito Tetsuya、Kuma Akiko、Sugiura Yuki、Ichimura Yoshinobu、Obata Miki、Kitamura Hiroshi、Okuda Shujiro、Lee Hyeon-Cheol、Ikeda Kazutaka、Kanegae Yumi、Saito Izumu、Auwerx Johan、Motohashi Hozumi、Suematsu Makoto、Soga Tomoyoshi、Yokomizo Takehiko、Waguri Satoshi、Mizushima Noboru、Komatsu Masaaki
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Journal Title
Nature Communications
Volume: 10
Issue: 1
Pages: 41467-41467
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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