Coordination of translational control and protein homeostasis during severe heat stress
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 thes...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 27, 2013
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| In: |
Current biology
Year: 2013, Volume: 23, Issue: 24, Pages: 2452-2462 |
| ISSN: | 1879-0445 |
| DOI: | 10.1016/j.cub.2013.09.058 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cub.2013.09.058 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0960982213012475 
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| Author Notes: | Valeria Cherkasov, Sarah Hofmann, Silke Druffel-Augustin, Axel Mogk, Jens Tyedmers, Georg Stoecklin, and Bernd Bukau |
| Summary: | 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. |
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| Item Description: | Gesehen am 13.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1879-0445 |
| DOI: | 10.1016/j.cub.2013.09.058 |