Functional analysis of sulfur metabolism and respiratory system: genome editing and energy metabolism analysis
Project/Area Number |
19K07341
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48040:Medical biochemistry-related
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 硫黄代謝 / エネルギー代謝 / ゲノム編集 / ミトコンドリア / 超硫黄分子 / 硫黄呼吸 / イオウ呼吸 |
Outline of Research at the Start |
アミノアシルtRNA酵素の一つであるシステイニルtRNA合成酵素(CARS)によって、ミトコンドリアにおいてシステインから合成されるイオウ代謝物が産生され、エネルギー代謝に関与することが示唆されている。応募者はこれらイオウ代謝に関連する酵素群の遺伝子改 変マウスを作製したところ胎生致死や短命などの表現型を示すことを見出した。このことからイオウ代謝酵素群はエネルギー代謝を調整することで発生時から成体での恒常性維持まで重要な役割を担っていると示唆される。今回応募者はイオウ代謝関連酵素群のゲノム編集マウスおよび線虫を作製・解析し、イオウ代謝の生体内における機能を分子レベルでのメカニズムを明らかにする。
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Outline of Final Research Achievements |
It has been suggested that cysteinyl-tRNA synthetase (CARS), one of the aminoacyl-tRNA enzymes, produces sulfur metabolites synthesized from cysteine in mitochondria and is involved in energy metabolism. The applicant generated mice genetically modified with these enzymes related to sulfur metabolism and found that they showed phenotypes such as embryonic lethality and short life span. This suggests that sulfur-metabolizing enzymes play an important role from development to adult homeostasis by regulating energy metabolism. In this study, the applicant will generate and analyze genome-edited mice and nematodes of sulfur metabolism-related enzymes to elucidate the mechanisms of sulfur metabolism in vivo at the molecular level.
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Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリアにおいてシステインから合成されるイオウ代謝物(パースルフィドなど)が、アミノアシルtRNA酵素の一つであるCARS2やSQRによって産生・代謝され、エネルギー代謝に関与することが示されている。このことは、生物が酸素のみならずイオウ代謝物を利用してエネルギー代謝を営むことを意味している。本研究で明らかになったCARS2およびSQR遺伝子改変マウスの解析により、発生および寿命に関する表現型が観察された。これらの結果はCARS、SQRなどの新規イオウ代謝酵素を介したイオウ依存型エネルギー代謝機構が個体発生から成体の恒常性維持まで広く、重要な役割を担っていることを示している。
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Report
(5 results)
Research Products
(31 results)
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[Journal Article] 8-Nitro-cGMP suppresses mineralization by mouse osteoblasts2022
Author(s)
Kaneko K, Miyamoto Y, Ida T, Morita M, Yoshimura K, Nagasaki K, Toba K, Sugisaki R, Motohashi H, Akaike T, Chikazu D, Kamijo R
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 71
Issue: 3
Pages: 191-197
DOI
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed / Open Access
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[Journal Article] Virucidal effect of monogalactosyl diacylglyceride from a green microalga, Coccomyxa sp. KJ, against clinical isolates of SARS-CoV-2 as assessed by a plaque assay.2021
Author(s)
Hayashi Kyoko, Asai Satomi, Umezawa Kazuo, Kakizoe Hidehumi, Miyachi Hayato, Morita Masanobu, Akaike Takaaki, Kuno Hitoshi, Komatsu Satoko, Watanabe Takumi, Kawahara Toshio.
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Journal Title
Journal of Clinical Laboratory Analysis
Volume: 36
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sulfide catabolism ameliorates hypoxic brain injury.2021
Author(s)
Marutani E, Morita M, Hirai S, Kai S, Grange RMH, Miyazaki Y, Nagashima F, Traeger L, Magliocca A, Ida T, Matsunaga T, Batten A, Li R, Tanaka T, Ikeda T, Nakagawa A, Atochin DN, Ihara H, Olenchock BA, Shen X, Nishida M, Hanaoka K, Kevil CG, Xian M, Bloch DB, Akaike T, Hindle AG, Motohashi H, Ichinose F, et al.
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 3108-3108
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation2021
Author(s)
Omori S, Tsugita M, Hoshikawa Y, Morita M, Ito F, Yamaguchi SI, Xie Q, Noyori O, Yamaguchi T, Takada A, Saitoh T, Toyokuni S, Akiba H, Nagata S, Kinoshita K, Nakayama M
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Journal Title
Cell reports
Volume: 34
Issue: 6
Pages: 108734-108734
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Methods in sulfide and persulfide research.2021
Author(s)
Takata Tsuyoshi, Jung Minkyung, Matsunaga Tetsuro, Ida Tomoaki, Morita Masanobu, Motohashi Hozumi, Shen Xinggui, Kevil Christopher G., Fukuto Jon M., Akaike Takaaki.
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Journal Title
Nitric Oxide
Volume: 116
Pages: 47-64
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Production of IL-17A at innate immune phase leads to decreased Th1 immune response and attenuated host defense against infection with Cryptococcus deneoformans2020
Author(s)
Sato K, Yamamoto H, Nomura T, Kasamatsu J, Miyasaka T, Tanno D, Matsumoto I, Kagesawa T, Miyahara A, Zong T, Oniyama A, Kawamura K, Yokoyama R, Kitai Y, Ishizuka S, Kanno E, Tanno H, Suda H, Morita M, Yamamoto M, Iwakura Y, Ishii K, Kawakami K
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Journal Title
The Journal of Immunology
Volume: 205
Issue: 3
Pages: 686-698
DOI
Related Report
Peer Reviewed
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[Presentation] Supersulfides Catalyze Nitric Oxide Metabolism via Glutathione-coupled Electron Transfer from Formaldehyde2022
Author(s)
Masanobu Morita, Tetsuro Matsunaga, Shingo Kasamatsu, Akira Nishimura, Md. Morshedul Alam, Kakeru Shimoda, Akiyuki Nishimura, Seiryo Ogata, Minkyung Jung, Tomoaki Ida, Motohiro Nishida, Hozumi Motohashi, Takaaki Akaike
Organizer
Gordon Research Conference
Related Report
Int'l Joint Research
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