HSF1 is required for induction of mitochondrial chaperones during the mitochondrial unfolded protein response
HSF1 is required for induction of mitochondrial chaperones during the mitochondrial unfolded protein response
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DOI：
10.1002/2211-5463.12863
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发表时间：
2020-05-15
期刊：
影响因子：
2.6
通讯作者：
Nakai, Akira
中科院分区：
文献类型：
--
作者：
Katiyar, Arpit;Fujimoto, Mitsuaki;Nakai, Akira
线粒体未折叠蛋白反应 (UPRmt) 的特点是线粒体伴侣和蛋白酶基因的转录诱导，以响应受损的线粒体蛋白质稳态，并在哺乳动物细胞中受到 ATF5 和 CHOP 的调节。然而，UPRmt 背后的详细机制目前尚不清楚。在这里，我们表明，在抑制基质伴侣 TRAP1、蛋白酶 Lon 或电子转移复合物 1 活性期间，HSF1 是激活小鼠胚胎成纤维细胞中线粒体伴侣基因（包括 HSP60、HSP10 和 mtHSP70）所必需的。 HSF1 与线粒体伴侣基因启动子组成型结合，我们观察到在 UPRmt 期间，其占据率在不同水平上显着增强。此外，HSF1 在相同条件下支持线粒体功能的维持。这些结果表明，HSF1 是 UPRmt 期间诱导线粒体伴侣所必需的，因此，它可能是线粒体蛋白质稳态受损条件下线粒体功能的守护者之一。
The mitochondrial unfolded protein response (UPRmt) is characterized by the transcriptional induction of mitochondrial chaperone and protease genes in response to impaired mitochondrial proteostasis and is regulated by ATF5 and CHOP in mammalian cells. However, the detailed mechanisms underlying the UPRmt are currently unclear. Here, we show that HSF1 is required for activation of mitochondrial chaperone genes, including HSP60, HSP10, and mtHSP70, in mouse embryonic fibroblasts during inhibition of matrix chaperone TRAP1, protease Lon, or electron transfer complex 1 activity. HSF1 bound constitutively to mitochondrial chaperone gene promoters, and we observed that its occupancy was remarkably enhanced at different levels during the UPRmt. Furthermore, HSF1 supported the maintenance of mitochondrial function under the same conditions. These results demonstrate that HSF1 is required for induction of mitochondrial chaperones during the UPRmt, and thus, it may be one of the guardians of mitochondrial function under conditions of impaired mitochondrial proteostasis.