Wu Rui, Tan Qunsong, Niu Kaifeng, Zhu Yuqi, Wei Di, Zhao Yongliang, Fang Hongbo
a Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
b University of Chinese Academy of Sciences, Beijing 100049, China.
Biochem Cell Biol. 2018 Feb;96(1):44-49. doi: 10.1139/bcb-2017-0149. Epub 2017 Oct 16.
MMS19 localizes to the cytoplasmic and nuclear compartments involved in transcription and nucleotide excision repair (NER). However, whether MMS19 localizes to mitochondria, where it plays a role in maintaining mitochondrial genome stability, remains unknown. In this study, we provide the first evidence that MMS19 is localized in the inner membrane of mitochondria and participates in mtDNA oxidative damage repair. MMS19 knockdown led to mitochondrial dysfunctions including decreased mtDNA copy number, diminished mtDNA repair capacity, and elevated levels of mtDNA common deletion after oxidative stress. Immunoprecipitation - mass spectrometry analysis identified that MMS19 interacts with ANT2, a protein associated with mitochondrial ATP metabolism. ANT2 knockdown also resulted in a decreased mtDNA repair capacity after oxidative damage. Our findings suggest that MMS19 plays an essential role in maintaining mitochondrial genome stability.
MMS19定位于参与转录和核苷酸切除修复（NER）的细胞质和细胞核区室。然而，MMS19是否定位于线粒体（其在线粒体基因组稳定性维持中发挥作用）仍不清楚。在本研究中，我们首次提供证据表明MMS19定位于线粒体内膜并参与线粒体DNA氧化损伤修复。MMS19基因敲低导致线粒体功能障碍，包括氧化应激后线粒体DNA拷贝数减少、线粒体DNA修复能力减弱以及线粒体DNA常见缺失水平升高。免疫沉淀-质谱分析确定MMS19与ANT2相互作用，ANT2是一种与线粒体ATP代谢相关的蛋白质。ANT2基因敲低也导致氧化损伤后线粒体DNA修复能力下降。我们的研究结果表明，MMS19在维持线粒体基因组稳定性中起重要作用。
