Coordination of Translational Control and Protein Homeostasis during Severe Heat Stress
Coordination of Translational Control and Protein Homeostasis during Severe Heat Stress
复制标题
DOI：
10.1016/j.cub.2013.09.058
复制
发表时间：
2013-12-16
期刊：
影响因子：
9.2
通讯作者：
Bukau, Bernd
中科院分区：
文献类型：
--
作者：
Cherkasov, Valeria;Hofmann, Sarah;Bukau, Bernd
背景资料：细胞暴露于严重的热应激不仅会导致蛋白质的错误折叠和聚集，而且还会抑制胞质热应激颗粒（heat-SG）中mRNA的翻译和储存，限制新合成的蛋白质流入过载的蛋白质组修复系统。这两种热应激反应是如何联系起来的尚不清楚。cerevisiae和D.黑腹果蝇热-SG含有mRNA、翻译机器组分（不包括核糖体）和分子伴侣，并且热-SG与错误折叠的、热不稳定的蛋白质的聚集体共组装。这些混合组件中的组件表现出不同的分子运动性，反映了差异捕获。我们表明，热SG拆卸和恢复的翻译活动在热应激恢复过程中是密切相关的解聚损坏的蛋白质存在于混合的组件，并需要热休克蛋白104和热休克蛋白70 activity.Conclusions：伴侣驱动的蛋白质解聚直接协调翻译重新启动的时间与蛋白质折叠能力在细胞蛋白质质量监测，使有效的蛋白质稳态。
Background: Exposure of cells to severe heat stress causes not only misfolding and aggregation of proteins but also inhibition of translation and storage of mRNA in cytosolic heat stress granules (heat-SGs), limiting newly synthesized protein influx into overloaded proteome repair systems. How these two heat stress responses connect is unclear.Results: Here, we show that both S. cerevisiae and D. melanogaster heat-SGs contain mRNA, translation machinery components (excluding ribosomes), and molecular chaperones and that heat-SGs coassemble with aggregates of misfolded, heat-labile proteins. Components in these mixed assemblies exhibit distinct molecular motilities reflecting differential trapping. We demonstrate that heat-SG disassembly and restoration of translation activity during heat stress recovery is intimately linked to disaggregation of damaged proteins present in the mixed assemblies and requires Hsp104 and Hsp70 activity.Conclusions: Chaperone-driven protein disaggregation directly coordinates timing of translation reinitiation with protein folding capacity during cellular protein quality surveillance, enabling efficient protein homeostasis.