Mitochondrial Gene Expression Changes in Normal and Mitochondrial Mutant Cells after Exposure to Ionizing Radiation
Mitochondrial Gene Expression Changes in Normal and Mitochondrial Mutant Cells after Exposure to Ionizing Radiation
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DOI：
10.1667/rr1737.1
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发表时间：
2010-05-01
影响因子：
3.4
通讯作者：
Tucker, James D.
中科院分区：
文献类型：
--
作者：
Kulkarni, Rohan;Marples, Brian;Tucker, James D.
线粒体DNA(MtDNA)包含13个基因，编码氧化磷酸化复合体的蛋白质，参与ATP的生成。Leber视神经萎缩和Leigh综合征是由线粒体基因组的点突变引起的疾病，其表型与能量缺乏有关。我们假设这些细胞中线粒体突变导致的能量缺乏会导致辐射过敏症。我们比较了两个线粒体突变细胞系GM13740(Leigh综合征)和GM10744(Leber视神经萎缩)和一个正常人淋巴母细胞系(GM-15036)在X射线照射(0-4Gy0-24小时)后13个线粒体蛋白编码基因的表达。基因表达的变化与细胞的放射敏感性进行比较。在与辐射敏感性变化相称的所有辐射剂量和时间内，Leigh综合征患者和正常细胞的线粒体基因表达在统计学上都有显著差异。这些数据表明，利综合征细胞修复辐射诱导的DNA损伤的能力受损，这导致了辐射过敏。这可能是由于线粒体基因表达减少和ATP生成减少导致的线粒体功能障碍，因为Leigh的视神经萎缩细胞表现出ATPase6基因的突变，ATPase6基因是ATP合成酶复合体V的重要组成部分。相反，Leber细胞的突变产生了辐射抗性，这可能归因于线粒体基因组中ND4基因的突变。线粒体突变细胞对电离辐射的敏感性改变可能会导致DNA修复能力下降，这可能会使携带mtDNA突变的个体面临更大的癌症和其他疾病风险。(C)2010年，由辐射研究学会提供
Mitochondrial DNA (mtDNA) contains 13 genes that encode proteins of the oxidative phosphorylation complex that are involved in ATP generation. Leber's optic atrophy and Leigh's syndrome are diseases that are caused by point mutations in the mitochondrial genome and that have phenotypes associated with energy deprivation. We hypothesized that energy deficiency from mitochondrial mutations in these cells leads to radiation hypersensitivity. Here we compared mitochondrial gene expression for the 13 mitochondrial protein-coding genes in two mitochondrial mutant cell lines, GM13740 (Leigh's syndrome) and GM10744 (Leber's optic atrophy) and a normal human lymphoblastoid cell line (GM 15036) after X irradiation (0-4 Gy) 0 to 24 h postirradiation. Changes in gene expression were compared with cellular radiosensitivity. Statistically significant differences between Leigh's syndrome and normal cells were found in mitochondrial gene expression for all radiation doses and times that were commensurate with changes in radiation sensitivity. The data suggest that Leigh's syndrome cells have an impaired ability to repair radiation-induced DNA damage that results in radiation hypersensitivity. This may be attributable to mitochondrial dysfunction from reductions in mitochondrial gene expression and ATP generation, since Leigh's optic atrophy cells exhibit a mutation in the ATPase6 gene, which is an important component of Complex V of ATP synthase. In contrast, the mutation of the Leber's cells conferred radioresistance, which might be attributed to the mutation in the ND4 gene in the mitochondrial genome. The altered sensitivity of mitochondrial mutant cells to ionizing radiation can lead to decreased DNA repair, which may put individuals with mtDNA mutations at greater risk for cancer and other diseases. (C) 2010 by Radiation Research Society