Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development
Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development
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DOI：
10.1073/pnas.1202367109
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发表时间：
2012-06-26
影响因子：
11.1
通讯作者：
Hayashi, Jun-Ichi
中科院分区：
文献类型：
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作者：
Hashizume, Osamu;Shimizu, Akinori;Hayashi, Jun-Ichi
据推测，由致病性线粒体DNA（mtDNA）突变的积累和由此产生的活性氧（ROS）或乳酸盐的过度产生引起的呼吸缺陷是衰老和年龄相关疾病（包括糖尿病和肿瘤发展）的原因。然而，没有直接证据证明mtDNA突变参与了这些过程，因为很难排除核DNA突变的可能参与。我们以前的研究通过使用mtDNA交换技术解决了这个问题，并表明在小鼠肿瘤细胞中发现的G13997 A mtDNA突变通过ROS过量产生诱导转移。在这里，使用transmitochondrial小鼠（mito-mice），我们已经产生了G13997 A mtDNA从小鼠肿瘤细胞到小鼠胚胎干细胞，我们提供了令人信服的证据支持上述假设的一部分，显示G13997 A mtDNA调节糖尿病的发展，淋巴瘤的形成和转移，但不老化，在这个模型。
It has been hypothesized that respiration defects caused by accumulation of pathogenic mitochondrial DNA (mtDNA) mutations and the resultant overproduction of reactive oxygen species (ROS) or lactates are responsible for aging and age-associated disorders, including diabetes and tumor development. However, there is no direct evidence to prove the involvement of mtDNA mutations in these processes, because it is difficult to exclude the possible involvement of nuclear DNA mutations. Our previous studies resolved this issue by using an mtDNA exchange technology and showed that a G13997A mtDNA mutation found in mouse tumor cells induces metastasis via ROS overproduction. Here, using transmitochondrial mice (mito-mice), which we had generated previously by introducing G13997A mtDNA from mouse tumor cells into mouse embryonic stem cells, we provide convincing evidence supporting part of the above mentioned hypothesis by showing that G13997A mtDNA regulates diabetes development, lymphoma formation, and metastasis-but not aging-in this model.