CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair.
CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair.
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DOI：
10.1016/j.celrep.2015.11.015
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发表时间：
2015-12-15
期刊：
影响因子：
8.8
通讯作者：
Li JJ
中科院分区：
文献类型：
--
作者：
Qin L;Fan M;Candas D;Jiang G;Papadopoulos S;Tian L;Woloschak G;Grdina DJ;Li JJ
核DNA修复能力是遗传毒性胁迫条件下细胞命运的关键决定因素。DNA修复是一个定义明确的能量消耗过程;然而，目前还不清楚DNA修复是如何被激发的，以及线粒体能量的产生是否有助于核DNA修复。在这里，我们报告了一个动态增强的耗氧量和线粒体ATP生成在辐射正常细胞，增加细胞周期激酶CDK 1和核DNA修复的线粒体搬迁。在携带CDK 1磷酸化缺陷突变体复合物I亚基的细胞中，基础和辐射诱导的线粒体ATP生成显著减少。类似地，线粒体ATP生成和核DNA修复也在含有细胞靶向激酶缺陷型CDK 1的细胞中严重受损。这些结果证明了一种控制线粒体和细胞核之间通信的机制，通过该机制，CDK 1促进线粒体生物能量学，以满足遗传毒性应激下DNA修复和细胞存活的细胞燃料需求增加。
Nuclear DNA repair capacity is a critical determinant of cell fate under genotoxic stress conditions. DNA repair is a well-defined energy consuming process; however, it is unclear how DNA repair is fueled and whether mitochondrial energy production contributes to nuclear DNA repair. Here, we report a dynamic enhancement of oxygen consumption and mitochondrial ATP generation in irradiated normal cells, paralleled with increased mitochondrial relocation of cell cycle kinase CDK1 and nuclear DNA repair. The basal and radiation-induced mitochondrial ATP generation is significantly reduced in cells harboring CDK1 phosphorylation deficient mutant complex I subunits. Similarly, mitochondrial ATP generation and nuclear DNA repair are also severely compromised in cells harboring mitochondrial-targeted kinase deficient CDK1. These results demonstrate a mechanism governing the communication between mitochondria and nucleus, by which CDK1 boosts mitochondrial bioenergetics to meet the increased cellular fuel demand for DNA repair and cell survival under genotoxic stress.