ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells
ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells
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DOI：
10.1016/j.bbamcr.2015.06.016
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发表时间：
2015-10-01
影响因子：
5.1
通讯作者：
Braun, Thomas
中科院分区：
文献类型：
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作者：
Al-Furoukh, Natalie;Ianni, Alessandro;Braun, Thomas
蛋白质稳态对生命至关重要，并由细胞伴侣和蛋白酶维持。一种主要的线粒体蛋白酶是ClpXP复合物，其由催化ClpX亚基和蛋白水解ClpP亚基组成。基于两个独立的观察，我们假设ClpX可能在ClpXP的细胞功能中起主导作用。因此，我们通过定量蛋白质组学分析了ClpX过表达对成肌细胞蛋白质组的影响。ClpX过表达导致线粒体标志物（蛋白质稳态途径，称为“线粒体未折叠蛋白反应”（UPRmt））的上调。虽然这种途径在秀丽隐杆线虫中有详细描述，但尚不清楚它是否在哺乳动物中保守。因此，我们将经典线虫UPRmt的特征与我们的哺乳动物ClpX触发的UPRmt数据集进行了比较。我们发现，它们共享相同的逆行性细胞核信号通路，涉及关键的UPRmt转录因子CHOP（也被称为Ddit3，CEBPZ或GADD153）。总之，我们的数据证实了哺乳动物UPRmt的存在，具有很大的相似性，线虫途径。此外，我们的研究结果表明，ClpX过表达是一个很好的和简单的模型来研究哺乳动物细胞中的UPRmt的潜在机制。(C)2015 Elsevier B.V.版权所有。
Proteostasis is crucial for life and maintained by cellular chaperones and proteases. One major mitochondrial protease is the ClpXP complex, which is comprised of a catalytic ClpX subunit and a proteolytic ClpP subunit. Based on two separate observations, we hypothesized that ClpX may play a leading role in the cellular function of ClpXP. Therefore, we analyzed the effect of ClpX overexpression on a myoblast proteome by quantitative proteomics.ClpX overexpression results in the upregulation of markers of the mitochondria( proteostasis pathway, known as the "mitochondrial unfolded protein response" (UPRmt). Although this pathway is described in detail in Caenorhabditis elegans, it is not clear whether it is conserved in mammals. Therefore, we compared features of the classical nematode UPRmt with our mammalian ClpX-triggered UPRmt dataset. We show that they share the same retrograde mitochondria-to-nucleus signaling pathway that involves the key UPRmt transcription factor CHOP (also known as Ddit3, CEBPZ or GADD153).In conclusion, our data confirm the existence of a mammalian UPRmt that has great similarity to the C elegans pathway. Furthermore, our results illustrate that ClpX overexpression is a good and simple model to study the underlying mechanisms of the UPRmt in mammalian cells. (C) 2015 Elsevier B.V. All rights reserved.