摘要
线粒体脱氧鸟苷激酶(dguok)缺失或者突变是造成线粒体DNA缺失综合征的主要原因.目前dguok在肿瘤发生和发展中的作用及机制尚未明确.我们发现在肺癌细胞中敲除dguok可以降低癌干细胞的球形成, dguok缺失不仅造成了线粒体形态改变,而且严重影响了线粒体的耗氧率(OCR).虽然dguok缺失可以造成线粒体DNA拷贝数的降低,但在肺癌细胞H1650中并没有显著降低线粒体DNA编码的基因的mRNA水平,蛋白质谱分析表明dguok缺失后显著降低线粒体复合体I组分NDUFB8的蛋白水平,但是并不影响ndufb8的mRNA水平,表明dguok缺失通过影响线粒体复合体I的组装来影响线粒体的功能及肿瘤的发生.
Deletion or mutation of mitochondrial deoxyguanosine kinase(dguok) is a major cause of mitochondrial DNA deletion syndrome.However, the role and mechanism of dguok in tumorigenesis have not been documented. We found that deletion of dguok in lung cancer H1650 cells reduced the Sphere formation, an indicator of cancer stem cell growth. dguok deletion not only caused the morphological changes of mitochondria, but also dramatically decreased the oxygen consumption rate(OCR). Although dguok deletion reduced the number of mitochondrial DNA copies, it did not significantly reduce the mRNA level of mitochondrial DNAcoding genes. Further analysis showed that dguok deletion considerably lowered the protein level of NDUFB8, a component of mitochondrial complex I, but did not affect the mRNA level of ndufb8. These findings suggested that dguok affected mitochondrial function and tumorigenesis through regulation of mitochondrial complex I level.
作者
孙瑞
胡元昭
商容磊
白韦钰
孙建伟
SUN Rui;HU YuanZhao;SHANG RongLei;BAI WeiYu;SUN JianWei(State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650091, China;Center for L Sciences, School of Life Sciences, Yunnan University, Kunming 650500, China;College of Life Sciences, South China Agricultural University, Guangzhou 510642, China)
出处
《中国科学：生命科学》
CSCD
北大核心
2019年第7期893-901,共9页
Scientia Sinica(Vitae)
基金
国家自然科学基金(批准号:31671448)资助
关键词
脱氧鸟苷激酶
线粒体
呼吸链复合体Ⅰ
肿瘤发生
deoxyguanosine kinase
mitochondria
mitochondrial complex Ⅰ
tumorigenesis
