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线粒体DNA的氧化损伤:活性氧生成增加的结果还是后果?

[Oxidative damage of mitochondrial DNA: the result or consequence of enhanced generation of reactive oxygen species].

作者信息

Płoszaj Tomasz, Robaszkiewicz Agnieszka, Witas Henryk

机构信息

Zakład Biologii Molekularnej, Uniwersytet Medyczny w Łodzi, Plac Hallera 1, 91-647 Łódź.

出版信息

Postepy Biochem. 2010;56(2):139-46.

Abstract

According to mitochondrial theory of ageing the ageing process results from accumulation of mitochondrial DNA (mtDNA) damage. Close vicinity of mtDNA molecule to the source of reactive oxygen species, electron transport chain, potentiates degradation of nucleic acid chemical components. The most common types of mtDNA damage generated are point mutations as a result of oxidative modifications of purines and pyrimidines (transitions as well as transversions), but also deletions and rarely insertions. Since mtDNA codes for subunits of respiratory chain enzymes, its lesions can alter homeostasis of the cell resulting in a decrease of intracellular ATP. Growing evidence indicates the role of mtDNA mutations in elevated production of reactive oxygen species, which in turn are proved to increase the number of mtDNA mutations. This mechanism gave the basis for theory of a vicious cycle: ROS<-->mutations of mtDNA

摘要

根据衰老的线粒体理论,衰老过程是由线粒体DNA(mtDNA)损伤的积累导致的。mtDNA分子与活性氧来源(电子传递链)的紧密相邻,增强了核酸化学成分的降解。产生的最常见的mtDNA损伤类型是由于嘌呤和嘧啶的氧化修饰导致的点突变(转换以及颠换),还有缺失,很少有插入。由于mtDNA编码呼吸链酶的亚基,其损伤会改变细胞的内环境稳定,导致细胞内ATP减少。越来越多的证据表明mtDNA突变在活性氧产生增加中所起的作用,而活性氧又被证明会增加mtDNA突变的数量。这一机制为恶性循环理论提供了基础:活性氧<-->mtDNA突变

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