Current approaches to reduce or eliminate mitochondrial DNA mutations  

作　　者：Liang Yang Tingfang Mei Xiaobing Lin Haite Tang Yi Wu Rui Wang Jinglei Liu Zahir Shah Xingguo Liu 

机构地区：[1]Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

出　　处：《Science China(Life Sciences)》2016年第5期532-535,共4页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China (2013CB967403, 2012CB721105);the ‘‘Strategic Priority Research Program’’ of the Chinese Academy of Sciences (XDA01020108);the National High-tech R&D Program (2012AA02A708);the National Natural Science Foundation projects of China (31271527, 81570520);Guangzhou Science and Technology Program (2014Y2-00161);Guangdong Natural Science Foundation for Distinguished Young Scientists (S20120011368);Guangdong Province Science and Technology Innovation Young Talents Program (2014TQ01R559);Guangdong Province Science and Technology Program (2015A020212031);the Ph D Start-up Fund of Natural Science Foundation of Guangdong Province (2014A030310071);the ‘‘One Hundred Talents’’ Project for Prof. Xingguo Liu from the Chinese Academy of Sciences

摘　　要：Mitochondrial DNA （mtDNA） mutations have been impli- cated in a broad range of disorders which severely affect human health （Wallace, 1999）. Some drugs have been developed to slow down pathological changes of mitochon- drial disorders. However, there is no effective treatment for patients with mtDNA mutations, mtDNA is less protected and has fewer repair mechanisms than nuclear DNA （nDNA）. Such a reality results in a much higher mutation rate in mtDNA than that in nDNA. The mixture of mutated mtDNA versus wild-type mtDNA is known as hetero- plasmy. Mitochondrial threshold effect refers to the fact that mtDNA mutation must accumulate to high proportions （60%-90%） before respiratory activity is affected （Schon et al., 2012）. It is feasible to selectively reduce the levels of mu- tated mtDNA while sparing wild-type mtDNA to skew this ratio back to a healthier range. Here, we describe the link between mtDNA mutation and mitochondrial diseases, and we summarize several newly developed approaches with regard to the reduction or elimination of mtDNA mutation in mammals. These methods include nuclear gene modula- tion, molecular approaches targeting mutated mtDNA, mtDNA replacement, and induced pluripotent stem cell （iPSC） modeling. These various methods have their own advantages and limitations.Mitochondrial DNA(mt DNA)mutations have been implicated in a broad range of disorders which severely affect human health(Wallace,1999).Some drugs have been developed to slow down pathological changes of mitochondrial disorders.However,there is no effective treatment for patients with mt DNA mutations.mt DNA is less protected and has fewer repair mechanisms than nuclear DNA(n DNA).Such a reality results in a much higher

关 键 词：线粒体DNA突变 基因突变 MTDNA突变 线粒体疾病 人类健康 核DNA 多能干细胞 病理变化 

分 类 号：R596[医药卫生—内科学]