MMS19 localizes to mitochondria and protects the mitochondrial genome from oxidative damage
MMS19 localizes to mitochondria and protects the mitochondrial genome from oxidative damage
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MMS19 定位于线粒体并保护线粒体基因组免受氧化损伤
DOI：
10.1139/bcb-2017-0149
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发表时间：
2018
影响因子：
2.9
通讯作者：
Fang Hongbo
中科院分区：
文献类型：
--
作者：
Wu Rui;Tan Qunsong;Niu Kaifeng;Zhu Yuqi;Wei Di;Zhao Yongliang;Fang Hongbo
MMS 19定位于参与转录和核苷酸切除修复（NER）的细胞质和核区室。然而，MMS 19是否定位于线粒体，在维持线粒体基因组稳定性方面发挥作用，仍然是未知的。在这项研究中，我们提供了第一个证据，MMS 19定位于线粒体内膜，并参与线粒体DNA氧化损伤修复。MMS 19敲低导致线粒体功能障碍，包括线粒体DNA拷贝数减少，线粒体DNA修复能力降低，以及氧化应激后线粒体DNA常见缺失水平升高。免疫沉淀-质谱分析鉴定MMS 19与ANT 2相互作用，ANT 2是与线粒体ATP代谢相关的蛋白质。ANT 2敲低也导致氧化损伤后mtDNA修复能力下降。我们的研究结果表明，MMS 19在维持线粒体基因组稳定性方面起着至关重要的作用。
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.