ClpP mediates activation of a mitochondrial unfolded protein response in C-elegans
ClpP mediates activation of a mitochondrial unfolded protein response in C-elegans
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DOI：
10.1016/j.devcel.2007.07.016
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发表时间：
2007-10-01
影响因子：
11.8
通讯作者：
Ron, David
中科院分区：
文献类型：
--
作者：
Haynes, Cole M.;Petrova, Kseniya;Ron, David
细胞对线粒体基质中未折叠和错误折叠蛋白质的反应知之甚少。在这里，我们报告了一个全基因组的RNAi为基础的筛选基因的信号线粒体未折叠蛋白反应（UPRmt）在C。优雅线粒体中未折叠的蛋白质应激与含同源结构域的转录因子DVE-1和小泛素样蛋白UBL-5之间的复合物形成相关，这两者都由UPRmt信号传导所需的基因编码。UPRmt的激活在时间和空间上与DVE-1的核再分布及其与线粒体伴侣基因启动子的增强结合相关。这些事件和下游UPRmt在clpp-1活性降低的动物中减弱，clpp-1编码与细菌ClpP同源的线粒体基质蛋白酶。由于已知ClpP在细菌热休克反应中起作用，我们的研究结果表明，真核生物利用来自原线粒体共生体的组分来发出UPRmt信号。
The cellular response to unfolded and misfolded proteins in the mitochondrial matrix is poorly understood. Here, we report on a genome-wide RNAi-based screen for genes that signal the mitochondrial unfolded protein response (UPRmt) in C. elegans. Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-fike protein UBL-5, both of which are encoded by genes required for signaling the UPRmt. Activation of the UPRmt correlates temporally and spatially with nuclear redistribution of DVE-1 and with its enhanced binding to the promoters of mitochondrial chaperone genes. These events and the downstream UPRmt are attenuated in animals with reduced activity of clpp-1, which encodes a mitochondrial matrix protease homologous to bacterial ClpP. As ClpP is known to function in the bacterial heat-shock response, our findings suggest that eukaryotes utilize component(s) from the protomitochondrial symbiont to signal the UPRmt.