Estrogen receptor mediates a distinct mitochondrial unfolded protein response
Estrogen receptor mediates a distinct mitochondrial unfolded protein response
复制标题
DOI：
10.1242/jcs.078220
复制
发表时间：
2011-05-01
影响因子：
4
通讯作者：
Germain, Doris
中科院分区：
文献类型：
--
作者：
Papa, Luena;Germain, Doris
内质网和线粒体基质的未折叠蛋白反应（UPRs）已被描述。在这里，我们发现乳腺癌细胞系MCF-7线粒体膜间空间（IMS）中蛋白质的积累激活了一个独特的UPR。在IMS应激下，活性氧（ROS）的过量产生和AKT的磷酸化触发雌激素受体（ER）活性，进而上调线粒体调节因子NRF1和IMS蛋白酶OMI（正式称为HTRA2）的转录。此外，我们证明了IMS应激诱导的UPR最终导致蛋白酶体活性增加。鉴于我们之前关于蛋白酶体和omi依赖性检查点限制IMS蛋白进口的报道，本研究的发现表明，这种新发现的UPR可作为克服IMS应激的细胞保护反应。
Unfolded protein responses (UPRs) of the endoplasmic reticulum and mitochondrial matrix have been described. Here, we show that the accumulation of proteins in the inter-membrane space (IMS) of mitochondria in the breast cancer cell line MCF-7 activates a distinct UPR. Upon IMS stress, overproduction of reactive oxygen species (ROS) and phosphorylation of AKT triggers estrogen receptor (ER) activity, which further upregulates the transcription of the mitochondrial regulator NRF1 and the IMS protease OMI (officially known as HTRA2). Moreover, we demonstrate that the IMS stress-induced UPR culminates in increased proteasome activity. Given our previous report on a proteasome-and OMI-dependent checkpoint that limits the import of IMS proteins, the findings presented in this study suggest that this newly discovered UPR acts as a cytoprotective response to overcome IMS stress.