PDF(Pubmed)
Abstract：
Mitochondria are key organelles for the optimal function of the cell. Among their many functions, they maintain protein homeostasis through their own proteostatic machinery, which involves proteases and chaperones that regulate protein import and folding inside mitochondria. In the early 2000s, the mitochondrial unfolded protein response (UPRmt) was first described in mammalian cells. This stress response is activated by the accumulation of unfolded/misfolded proteins within the mitochondrial matrix, which results in the transmission of a signal to the nucleus to increase the expression of proteases and chaperones to address the abnormal mitochondrial protein load. After its discovery, this retrograde signaling pathway has also been described in other organisms of different complexities, suggesting that it is a conserved stress response. Although there are some specific differences among organisms, the mechanism of this stress response is mostly similar and involves the transmission of a signal from mitochondria to the nucleus that induces chromatin remodeling to allow the binding of specific transcription factors to the promoters of chaperones and proteases. In the last decade, proteins and signaling pathways that could be involved in the regulation of the UPRmt, including the Wnt signaling pathway, have been described. This minireview aims to summarize what is known about the mechanism of the UPRmt and its regulation, specifically in mammals and C. elegans.
摘要：
线粒体是细胞最佳功能的关键细胞器。在其众多功能中,它们通过自己的蛋白质稳定机制维持蛋白质的稳态，其中涉及调节线粒体内蛋白质导入和折叠的蛋白酶和伴侣。在2000年代初期，线粒体未折叠蛋白反应(UPRmt)首先在哺乳动物细胞中被描述.这种应激反应是通过线粒体基质内未折叠/错误折叠蛋白质的积累而激活的。这导致信号传递到细胞核，以增加蛋白酶和伴侣的表达，以解决异常的线粒体蛋白负荷。在它被发现之后,这种逆行信号通路也在其他复杂的生物体中被描述，这表明这是一种保守的应激反应。尽管生物体之间存在一些特定的差异，这种应激反应的机制大多相似，涉及信号从线粒体传递到细胞核，诱导染色质重塑，以允许特定转录因子与伴侣和蛋白酶的启动子结合。在过去的十年里，可能参与UPRmt调节的蛋白质和信号通路，包括Wnt信号通路,已被描述。这篇小型综述旨在总结人们对UPRmt及其调控机制的了解，特别是在哺乳动物和秀丽隐杆线虫中。
