Studies on skeletal muscle fiber-type specific responses to pathogenic mtDNA
| Project/Area Number |
16K14719
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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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 |
NAKADA Kazuto 筑波大学, 生命環境系, 教授 (80323244)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ミトコンドリア / ミトコンドリアDNA / 突然変異 / 骨格筋 / インスリンシグナル / ミトコンドリア病 / モデルマウス / ミトコンドリアゲノム / 細胞分化 / エネルギー代謝 |
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| Outline of Final Research Achievements |
To examine mechanisms for cell-type specific sensitivities to mutant mitochondrial DNA (mtDNA), we used model mice heteroplasmic for wild-type mtDNA and pathogenic mtDNA with a deletion (del-mtDNA). In skeletal muscles with a high loads of del-mtDNA, mitochondrial respiration defects observed in slow oxidative type 1 and fast oxido-glycolytic type 2A/2X fibers, but not in fast glycolytic type 2B fibers that the relocation of glucose transporter 4 (GULT4) to sarcolemma from cytoplasm was accelerated. Chemical deconditioning of the relocation of GLUT4 induced mitochondrial respiration defects in 2B fiber and creation of ragged-red fibers in fast muscle tissues. Our findings indicated that relocation of GLUT4 in skeletal muscle fibers is necessary for tolerance to accumulation of del-mtDNA and also suggested that controls of insulin signaling via GULT4 would be a target for recovering mitochondrial respiration defects of cells with oxidative property in mtDNA-mediated disorders.
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Report
(3 results)
Research Products
(11 results)
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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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