摘要
能量代谢重编程是肿瘤细胞一个重要的标志特征,而由线粒体DNA(mitochondrial DNA,mtDNA)结构及功能异常引起的线粒体功能障碍是其机制之一。人类mtDNA为位于线粒体基质中由16569bp组成的双链闭合环状分子,编码与氧化磷酸化电子传递链相关的13种多肽以及与线粒体蛋白合成相关的22种tRNA和2种rRNA。近年来,人们发现多种肿瘤组织及细胞中存在mtDNA序列的多类型突变或拷贝数的变异,且mtDNA的这些异常与肿瘤的发生发展、早期诊断及放化疗监测等密切相关。异常的mtDNA因削弱线粒体产能、增加细胞内活性氧(reactive oxygen species,ROS)水平、打破Ca2+稳态,从而赋予肿瘤细胞代谢重编程、凋亡抵抗等侵袭性进程。针对mtDNA异常在肿瘤发生发展中的作用及机制研究,将为肿瘤的早期诊断及靶向治疗提供新的策略。
Energy metabolism reprogramming was recently identified as one of the important cancer hall- marks. One of the underlying mechanisms is mitochondrial dysfunction caused by the disorders of structure and function in mitoehondrial DNA. Human mtDNA is located in the mitochondrial matrix and it is a circular, double-stranded molecule of 16 569 base pairs in length. It encodes 13 polypeptides of the enzyme complexes of the electron transport chain, 22 transfer RNAs and 2 ribosomal RNAs for mitochondrial protein synthesis. Recently, several types of somatic mtDNA sequence mutations and copy number alterations have been iden- tified in many tumors and they correlate strongly with the carcinogenesis, progression, early diagnosis and monitoring of radiotherapy and chemotherapy of tumors. Abnormality of mitochondrial DNA may lead to mitochondrial dysfunction, increase reactive oxygen species of cells, break intracellular calcium homeostasis, thus conferring cancer ceils the ability to reprogram metabolism, resist apoptosis and invade. Research on mi- tochondrial alterations in tumor cells development might be a promising strategy for the development of early diagnosis and selective therapy.
出处
《生命的化学》
CAS
CSCD
2016年第6期862-867,共6页
Chemistry of Life
关键词
线粒体DNA
肿瘤
突变
拷贝数
mitochondrial DNA
tumor
mutations
copy number
