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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."xsd:string
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http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/author"Stoecklin G."xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/author"Hofmann S."xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/author"Bukau B."xsd:string
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http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/author"Druffel-Augustin S."xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/author"Tyedmers J."xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/author"Cherkasov V."xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/name"Curr Biol"xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/pages"2452-2462"xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/title"Coordination of translational control and protein homeostasis during severe heat stress."xsd:string
http://purl.uniprot.org/citations/24291094http://purl.uniprot.org/core/volume"23"xsd:string
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