Segregation mechanism of human mitochondrial genome through TFAM
Project/Area Number |
24790324
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pathological medical chemistry
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Research Institution | Jichi Medical University |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | ミトコンドリアDNA / 分配 / TFAM / ミトコンドリア / ヌクレオイド |
Outline of Final Research Achievements |
The segregation of mitochondrial genome affects the transmission of mutant mitochondrial DNA (mtDNA) variant and clinical abnormalities of mitochondrial disorders. Recently, we clarified that human mitochondrial transcription factor A (TFAM) is required for equal distribution and symmetric segregation of mtDNA in cultured cells. To elucidate the molecular mechanism of the TFAM-mediated mtDNA segregation, we screened nucleoid factors involved in this process. We found a mitochondrial AAA+ chaperone Clp as a novel regulator. Because ClpX enhances the DNA-binding activity of TFAM in vitro, it is strongly suggested that ClpX regulates mtDNA segregation through quality control of TFAM. By using separated fluorescent protein as reporter, we found that TFAM self-associates in mitochondria in vivo. The dimer mutant is actively degraded by proteasome system, suggesting that the self-interaction protects TFAM from degradation and regulates its expression levels.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Translational repression of the McKusick-Kaufman syndrome transcript by unique upstream open reading frames encoding mitochondrial proteins with alternative polyadenylation sites2013
Author(s)
Akimoto, C. Sakashita, E., Kasashima, K., Kuroiwa, K., Tominaga, K., Hamamoto, T., and Endo, H.
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Journal Title
Biochem Biophys Acta
Volume: 1830
Issue: 3
Pages: 2728-2738
DOI
Related Report
Peer Reviewed
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[Journal Article] Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type2013
Author(s)
Tetsuka, S. Tominaga, K. Ohta, E. Kuroiwa, K. Sakashita, E. Kasashima, K. Hamamoto, T. Namekawa, M. Morita, M. Natsui, S. Morita, T. Tanaka, K. Takiyama, Y. Nakano, I. Endo, H.
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Journal Title
J Neurol Sci
Volume: 335
Issue: 1-2
Pages: 48-57
DOI
Related Report
Peer Reviewed
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