应激相关激活转录因子-1调节线粒体非折迭蛋白反应.docxVIP

6月15日，Science在线报道应激相关激活转录因子-1进入线粒体的效率可调节线粒体非折叠蛋白反应的水平。为了更好地理解线粒体功能障碍的反应，研究者研究了，应激相关激活转录因子-1（ATFS-1）感受线粒体应激过程，及其在线粒体非折叠蛋白反应（UPRmt）条件下与细胞核通信的机制。研究发现，调控的关键点是ATFS-1进入线粒体的效率。除了一个核定位序列，ATFS-1还有一个氨基端的线粒体定位序列。这是UPRmt抑制反 应所必不可少的。通常情况下，ATFS-1被导入到线粒体并降解。然而，在线粒体应激情况下，ATFS-1进入线粒体效率下降，使其相当一部分积聚在细胞 质并转移到细胞核中。该研究结果表明，细胞通过ATFS-1监测线粒体蛋白输入效率，进而利用保护性转录反应协调线粒体功能障碍的水平。（生物谷）doi:10.1016/j.cell.2011.10.017PMC:PMID:Mitochondrial Import Efficiency of ATFS-1 Regulates Mitochondrial UPR ActivationAmrita M. Nargund1,*, Mark W. Pellegrino1,*, Christopher J. Fiorese1,2, Brooke M. Baker1, Cole M. HaynesTo better understand the response to mitochondrial dysfunction, we examined the mechanism by which Activating Transcription Factor associated with Stress-1 (ATFS-1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPRmt). We found that the key point of regulation was the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an amino-terminal mitochondrial targeting sequence, which was essential for UPRmt repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, import efficiency was reduced, allowing a percentage of ATFS-1 to accumulate in the cytosol and traffic to the nucleus. Our results show that cells monitor mitochondrial import efficiency via ATFS-1 to coordinate the level of mitochondrial dysfunction with the protective transcriptional response.