ATFS-1 的线粒体导入效率调节线粒体 UPR 的激活。
Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.
机构信息
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
出版信息
Science. 2012 Aug 3;337(6094):587-90. doi: 10.1126/science.1223560. Epub 2012 Jun 14.
Abstract
To better understand the response to mitochondrial dysfunction, we examined the mechanism by which ATFS-1 (activating transcription factor associated with stress-1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans. We found that the key point of regulation is the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an N-terminal mitochondrial targeting sequence that is essential for UPR(mt) repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, we found that 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.
摘要
为了更好地理解对线粒体功能障碍的反应，我们研究了 ATFS-1（与应激相关的激活转录因子 1）在秀丽隐杆线虫的线粒体未折叠蛋白反应 (UPR(mt)) 期间如何感知线粒体应激并与核通讯的机制。我们发现，调节的关键点是 ATFS-1 的线粒体导入效率。除了核定位序列外，ATFS-1 还具有 N 端线粒体靶向序列，该序列对于 UPR(mt) 抑制是必需的。正常情况下，ATFS-1 被导入线粒体并降解。然而，在线粒体应激期间，我们发现导入效率降低，导致一部分 ATFS-1 在细胞质中积累并转运到核内。我们的结果表明，细胞通过 ATFS-1 监测线粒体导入效率，以协调线粒体功能障碍的程度与保护性转录反应。
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