期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/ijms20133302
关键词
mtDNA repair; mtDNA content; OGG1 knockout (ko); NTH1 ko; 8-oxoG localization
资金
- MIUR-FFABR 2018
- Istituto Banco di Napoli Fondazione 2015
- Intramural Program of the National Institutes on Aging, National Institute of Health, USA
- NATIONAL INSTITUTE ON AGING [ZIAAG000733, ZIAAG000727] Funding Source: NIH RePORTER
Mitochondrial oxidative stress accumulates with aging and age-related diseases and induces alterations in mitochondrial DNA (mtDNA) content. Since mtDNA qualitative alterations are also associated with aging, repair of mtDNA damage is of great importance. The most relevant form of DNA repair in this context is base excision repair (BER), which removes oxidized bases such as 8-oxoguanine (8-oxoG) and thymine glycol through the action of the mitochondrial isoform of the specific 8-oxoG DNA glycosylase/apurinic or apyrimidinic (AP) lyase (OGG1) or the endonuclease III homolog (NTH1). Mouse strains lacking OGG1 (OGG1(-/-)) or NTH1 (NTH1(-/-)) were analyzed for mtDNA alterations. Interestingly, both knockout strains presented a significant increase in mtDNA content, suggestive of a compensatory mtDNA replication. The mtDNA common deletion was not detected in either knockout mouse strain, likely because of the young age of the mice. Formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites accumulated in mtDNA from OGG1(-/-) but not from NTH1(-/-) mice. Interestingly, the D-loop region was most severely affected by the absence of OGG1, suggesting that this region may be a hotspot for oxidative damage. Thus, we speculate that mtDNA alterations may send a stress message to evoke cell changes through a retrograde mitochondrial-nucleus communication.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据