Mitochondrial oxidative stress can lead to nuclear hypermutability
Mitochondrial oxidative stress can lead to nuclear hypermutability
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DOI：
10.1016/j.mad.2004.02.007
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
Ishii, N
中科院分区：
文献类型：
--
作者：
Hartman, P;Ponder, R;Ishii, N
活性氧（ROS）在线粒体中产生，并且被认为在衰老、致癌和其他病理学的发展中是重要的。我们现在提供了直接的实验证据，将线粒体ROS的产生与诱导核DNA损伤和随后的染色体基因突变联系起来。具体而言，我们证明了秀丽隐杆线虫的mev-1突变体在其染色体DNA中具有升高的氧化损伤水平。该突变体先前被证明在其线粒体中过度产生ROS。我们还表明，突变频率较高的mev-1突变体在缺氧条件下比野生型菌株。延伸开来。这些数据表明，来源于尿道的ROS使其它基因突变，包括肿瘤抑制基因和癌基因。我们认为这三步过程（线粒体ROS ->核DNA损伤->突变）有助于衰老和年龄相关疾病。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Reactive oxygen species (ROS) are generated in mitochondria and are thought to be important in aging, carcinogenesis, and the development of other pathologies. We now provide direct experimental evidence linking mitochondrial ROS generation to the induction of nuclear DNA damage and subsequent mutagenesis of a chromosomal gene. Specifically, we demonstrate that the mev-1 mutant of Caenorhabditis elegans has elevated levels of oxidative damage in its chromosomal DNA. This mutant was shown previously to overproduce ROS in its mitochondria. We also show that mutation frequencies were higher in the mev-1 mutant under hypoxia than in the wild type strain. By extension. these data imply that mitochondrially derived ROS mutate other genes, including tumor suppressor genes and oncogenes. We propose that this three-step process (mitochondrial ROS --> nuclear DNA damage --> mutation) contributes to aging and age-associated diseases. (C) 2004 Elsevier Ireland Ltd. All rights reserved.