Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity.
Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity.
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DOI：
10.1038/ncomms7580
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发表时间：
2015-03-12
影响因子：
16.6
通讯作者：
Nakai A
中科院分区：
文献类型：
--
作者：
Tan K;Fujimoto M;Takii R;Takaki E;Hayashida N;Nakai A
热休克反应是哺乳动物对包括热休克在内的蛋白毒性应激的一种适应性反应，受热休克因子1（HSF 1）的调节。蛋白毒性应激挑战包括线粒体在内的所有亚细胞区室。因此，线粒体信号与HSF 1的活性之间存在密切联系。在这里，我们表明，热休克触发线粒体SSBP 1，这是参与线粒体DNA的复制，在依赖于线粒体渗透性转换孔ANT-VDAC 1复合物和直接与HSF 1相互作用的方式核转位。HSF 1将SSBP 1募集到编码细胞质/核和线粒体伴侣的基因的启动子。然后，HSF 1-SSBP 1复合物通过促进染色质重塑因子BRG 1的募集来增强它们的诱导，并支持细胞存活和维持线粒体膜电位对抗蛋白毒性应激。这些结果表明，线粒体SSBP 1的核转位是调节细胞质/核和线粒体蛋白质稳态对抗蛋白毒性应激所必需的。 热休克诱导蛋白毒性应激，细胞反应由热休克因子1（HSF 1）介导。在这里，Tan等人表明，热休克后，线粒体SSBP 1易位到细胞核并结合HSF 1，以增强伴侣蛋白的表达并支持线粒体功能的维持。
Heat-shock response is an adaptive response to proteotoxic stresses including heat shock, and is regulated by heat-shock factor 1 (HSF1) in mammals. Proteotoxic stresses challenge all subcellular compartments including the mitochondria. Therefore, there must be close connections between mitochondrial signals and the activity of HSF1. Here, we show that heat shock triggers nuclear translocation of mitochondrial SSBP1, which is involved in replication of mitochondrial DNA, in a manner dependent on the mitochondrial permeability transition pore ANT–VDAC1 complex and direct interaction with HSF1. HSF1 recruits SSBP1 to the promoters of genes encoding cytoplasmic/nuclear and mitochondrial chaperones. HSF1–SSBP1 complex then enhances their induction by facilitating the recruitment of a chromatin-remodelling factor BRG1, and supports cell survival and the maintenance of mitochondrial membrane potential against proteotoxic stresses. These results suggest that the nuclear translocation of mitochondrial SSBP1 is required for the regulation of cytoplasmic/nuclear and mitochondrial proteostasis against proteotoxic stresses. Heat shock induces proteotoxic stress, and the cellular response is mediated by heat-shock factor 1 (HSF1). Here, Tan et al. show that following heat shock, mitochondrial SSBP1 translocates to the nucleus and binds HSF1 to enhance the expression of chaperones and support the maintenance of mitochondrial function.