Endoplasmic reticulum (ER) stress induces the repression of protein synthesis throughout the cell. Attempts to understand how localized stress leads to widespread repression have been limited by difficulties in resolving translation rates at the subcellular level. Here, using live-cell imaging of reporter mRNA translation, we unexpectedly found that during ER stress, active translation at mitochondria was significantly protected. The mitochondrial protein ATPase family AAA domain-containing protein 3A (ATAD3A) interacted with protein kinase RNA–like endoplasmic reticulum kinase (PERK) and mediated this effect on localized translation by competing for binding with PERK’s target, eukaryotic initiation factor 2 (eIF2). PERK-ATAD3A interactions increased during ER stress, forming mitochondria-ER contact sites. Furthermore, ATAD3A binding attenuated local PERK signaling and rescued the expression of some mitochondrial proteins. Thus, PERK-ATAD3A interactions can control translational repression at a subcellular level, mitigating the impact of ER stress on the cell.

中文翻译：

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PERK-ATAD3A 相互作用为 ER 应激期间的蛋白质合成提供了亚细胞安全港


内质网 (ER) 应激会抑制整个细胞的蛋白质合成。由于在亚细胞水平上解析翻译速率的困难，了解局部压力如何导致广泛的抑制的尝试受到限制。在这里，使用报告基因 mRNA 翻译的活细胞成像，我们意外地发现，在内质网应激期间，线粒体的主动翻译受到显着保护。线粒体蛋白 ATP 酶家族 AAA 结构域蛋白 3A (ATAD3A) 与蛋白激酶 RNA 样内质网激酶 (PERK) 相互作用，并通过与 PERK 的靶标真核起始因子 2 (eIF2) 竞争结合来介导这种对局部翻译的影响。 PERK-ATAD3A 相互作用在内质网应激期间增加，形成线粒体-内质网接触位点。此外，ATAD3A 结合减弱了局部 PERK 信号传导并挽救了一些线粒体蛋白的表达。因此，PERK-ATAD3A 相互作用可以控制亚细胞水平的翻译抑制，减轻 ER 应激对细胞的影响。