线粒体DNA控制区研究进展

Advances in mitochondrial DNA control region

哺乳动物线粒体DNA(mitochondrialDNA,mtDNA)控制区由中央保守区、ETAS区和CSB区构成。近十年的研究发现线粒体基因组的缺陷和衰老、肿瘤、神经退行性疾病、肌病、心肌病以及糖尿病的关系密切。由于控制区调控整个线粒体DNA的复制和转录,因此,该区的碱基突变可能引起线粒体DNA复制和转录速度加快,造成突变的线粒体DNA相对增多,经过长期的累积可能导致肿瘤的发生。过去的研究主要注重线粒体的形态结构和能量代谢的异常,近年来研究发现控制区某些区段的突变率是核基因组的100～200倍。因此,控制区的突变在肿瘤发生中的作用和地位越来越受到重视。mtDNA的拷贝数远高于nDNA,它的突变较容易被检测到。因此,寻找与特定肿瘤相关的特异性mtDNA控制区突变成为近年来研究的热点之一。

Mammalian Mitochondrial DNA （mtDNA） control region consists of central domain, ETAS domain and CSB domain. The last ten years＇ studies showed that the genetic defect of mtDNA had a close relation with aging, tumorigenesis, neurodegenerative disorders, myopathy, cardiomyopathy and diabetes. MtDNA control region contains the major regulatory elements for the replication and transcription of the mtDNA, so mutations of this region could accelerate the copy and transcription of mtDNA, leading to the comparatively increase in the number of the mutated mtDNA, which, in the long run, results in the tumorigenesis. As far as tumor is concerned, researchers used to focus on the mitochondrial abnormalities in conformation, structure and energetic metabolism. In the recent years, it is known that for some D-loop regions, the rate of mtDNA mutations may reach 100-200-fold higher levels than those of nuclear DNA. So, recently, more and more emphases were put on the role of mtDNA control region in tumorigenesis. As the copy number of mtDNA is much higher than that of nDNA, and its mutation could be detected more easily, and to find the specific mtDNA mutations in tumors became one of the recent research highlights.