Polymorphic mutations in mouse mitochondrial DNA regulate a tumor phenotype
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- 作者：Gaku Takibuchi ; Hirotake Imanishi ; Mami Morimoto ; Kaori Ishikawa ; Kazuto Nakada ; Noriko Toyama-Sorimachi ; Yoshiaki Kikkawa ; Keizo Takenaga ; Jun-Ichi Hayashi
- 关键词：Transmitochondrial cybrids ; Mouse C3H mtDNA ; Polymorphic mtDNA mutations ; Tumor phenotypes ; Hypoxia sensitivity
- 刊名：Mitochondrion
- 出版年：November, 2013
- 年：2013
- 卷：13
- 期：6
- 页码：881-887
- 全文大小：870 K
文摘
To examine whether polymorphic mtDNA mutations that do not induce significant respiration defects regulate phenotypes of tumor cells, we used mouse transmitochondrial tumor cells (cybrids) with nuclear DNA from C57BL/6 (B6) strain and mtDNA from allogenic C3H strain. The results showed that polymorphic mutations of C3H mtDNA in the cybrids induced hypoxia sensitivity, resulting in a delay of tumor formation on their subcutaneous inoculation into B6 mice. Therefore, the effects of polymorphic mutations in normal mtDNA have to be carefully considered, particularly when we apply the gene therapy to the embryos to replace their pathogenic mtDNA by normal mtDNA.