2014 Fiscal Year Final Research Report
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 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | ミトコンドリアDNA / 分配 / TFAM |
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| 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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| Free Research Field |
分子生物学
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