RecQL4 regulates autophagy and apoptosis in U2OS cells
RecQL4 regulates autophagy and apoptosis in U2OS cells
复制标题
DOI：
10.1139/bcb-2016-0005
复制
发表时间：
2016-12-01
影响因子：
2.9
通讯作者：
Fang, Hongbo
中科院分区：
文献类型：
--
作者：
Duan, Yangmiao;Fang, Hongbo
RecQL 4是5种人类RecQ解旋酶之一，是基因组稳定性的关键介质，其缺陷可导致过早衰老表型。在这里，通过使用CRISPR/Cas和RNAi技术，我们证明了与对照细胞相比，RecQL 4敲低和敲除细胞中的自噬水平均升高。令人惊讶的是，与对照细胞相比，在RecQL 4敲除细胞中线粒体含量增加，并且LC 3与线粒体的共定位部分丧失，表明RecQL 4缺乏损害了U2 OS细胞中的线粒体吞噬过程。此外，我们发现RecQL 4的敲除使PINK 1不稳定。此外，RecQL 4敲除细胞在线粒体应激下比对照细胞更容易发生凋亡。总之，我们的研究结果表明RecQL 4在U2 OS细胞中调节自噬/线粒体自噬中的新作用。
RecQL4, one of the 5 human RecQ helicases, is a key mediator of genomic stability and its deficiency can cause premature aging phenotypes. Here, by using CRISPR/Cas and RNAi technology, we demonstrated that autophagy level was elevated in both RecQL4 knockdown and knockout cells compared with those of the control cells. Surprisingly, mitochondrial content was increased and LC3 co-localization with mitochondria was partially lost in RecQL4 knockout cells compared with the control cells, suggesting that RecQL4 deficiency impaired mitophagic processes in U2OS cells. Furthermore, we found that knockout of RecQL4 destabilized PINK1. In addition, RecQL4 knockout cells were more susceptible to apoptosis under mitochondrial stress than the control cells. In conclusion, our findings indicated a novel role of RecQL4 in the regulation of autophagy/mitophagy in U2OS cells.