...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell metabolism >Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice.
【24h】

Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice.

机译：对蛋白质编码基因有重大影响的随机点突变是mtDNA突变小鼠过早衰老的驱动力。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The mtDNA mutator mice have high levels of point mutations and linear deletions of mtDNA causing a progressive respiratory chain dysfunction and a premature aging phenotype. We have now performed molecular analyses to determine the mechanism whereby these mtDNA mutations impair respiratory chain function. We report that mitochondrial protein synthesis is unimpaired in mtDNA mutator mice consistent with the observed minor alterations of steady-state levels of mitochondrial transcripts. These findings refute recent claims that circular mtDNA molecules with large deletions are driving the premature aging phenotype. We further show that the stability of several respiratory chain complexes is severely impaired despite normal synthesis of the corresponding mtDNA-encoded subunits. Our findings reveal a mechanism for induction of aging phenotypes by demonstrating a causative role for amino acid substitutions in mtDNA-encoded respiratory chain subunits, which, in turn, leads to decreased stability of the respiratory chain complexes and respiratory chain deficiency.
机译：mtDNA突变小鼠具有高水平的点突变和mtDNA线性缺失，从而导致进行性呼吸链功能障碍和过早的衰老表型。现在，我们已经进行了分子分析，以确定这些mtDNA突变削弱呼吸链功能的机制。我们报告线粒体蛋白质合成在mtDNA突变小鼠中不受损害，与观察到的线粒体转录本稳态水平的微小变化一致。这些发现反驳了最近的说法，即具有大量缺失的环状mtDNA分子正在驱动过早的表型。我们进一步表明，尽管正常合成了相应的mtDNA编码的亚基，但几个呼吸链复合物的稳定性严重受损。我们的发现揭示了通过证明mtDNA编码的呼吸链亚基中氨基酸取代的致病作用来诱导衰老表型的机制，进而导致呼吸链复合物的稳定性降低和呼吸链缺乏。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号