An approach from crosstalks of nuclei-mitochondria to disease mechanisms of mitochondrial diseases
| Project/Area Number |
16K18535
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cell biology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ミトコンドリアDNA / ミトコンドリア・ダイナミクス / Drp1 / ミトコンドリア分裂 / ミトコンドリア病 / 病態発症機構 / ミトコンドリア / mtDNA / 呼吸機能 / 貧血 / 血球分化 / モデルマウス / ΔmtDNA / Mitophagy |
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| Outline of Final Research Achievements |
Disease phenotypes of the model mice with a pathogenic mitochondrial DNA (mtDNA) mutation and dysfunction of Drp1, a mitochondrial fission factor, were analyzed. Drp1 dysfunction made disease phenotypes induced by the mtDNA mutation more severer. These results indicate that Drp1-mediated mitohondrial fission suppresses disease phenotypes induced by the mtDNA mutation, and also suggest that there are important crosstalks between mitochondria and nuclei.
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| Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリア病はその病態発症機構がほとんど理解されておらず、治療法はおろか正確な診断すらもままならない困難な疾患である。本研究は、ミトコンドリアDNA（mtDNA）に突然変異を有することで病態を発症するマウスに、核DNAにコードされたミトコンドリア関連遺伝子の機能不全を共存させることによって、核DNAのミトコンドリア関連遺伝子とミトコンドリア機能との間にクロストークがあることを見出した。この成果は、ミトコンドリア病の複雑な病態発症機構の一端を明らかにすることにつながると考えられる。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] An administration of TAK-683 at a minimally effective dose for luteinizing hormone stimulation under the absence of the ovary induces luteinizing hormone surge in ovary-intact goats2017
Author(s)
Kanai N, Endo N, Ohkura S, Wakabayashi Y, Matsui H, Matsumoto H, Ishikawa K, Tanaka A, Watanabe T, Okamura H, Tanaka T.
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Journal Title
Journal of Reproduction and Development
Volume: 63
Issue: 3
Pages: 305-310
DOI
NAID
ISSN
0916-8818, 1348-4400
Related Report
Peer Reviewed
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[Journal Article] A novel mutation in TAZ causes mitochondrial respiratory chain disorder without cardiomyopathy2016
Author(s)
Borna NN, Kishita Y, Ishikawa K, Nakada K, Hayashi JI, Tokuzawa Y, Kohda M, Nyuzuki H, Yamashita-Sugahara Y, Nasu T, Takeda A, Murayama K, Ohtake A, Okazaki Y
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Journal Title
J Hum Genet
Volume: 62
Issue: 5
Pages: 539-547
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] The importance of mitochondrial fission in preventing disease phenotypes induced by a pathogenic mtDNA mutation.2016
Author(s)
Ishikawa K, Katada S, Ogasawara E, Homma Y, Ishihara T, Mito T, Mihara K, Hayashi JI, Ishihara N, Nakada K.
Organizer
The 13th Conference of Asian Society for Mitochondrial Research and Medicine [ASMRM] and The 16th Conference of Japanese Siciety of Mitochondrial Research and Medicine [J-mit].
Place of Presentation
TKPガーデンシティ品川, Shinagawa, Tokyo, Japan.
Year and Date
2016-10-30
Related Report
Int'l Joint Research
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