title: Coordination of translational control and protein homeostasis during severe heat stress.
abstract: 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.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cherkasov
authors.affiliation: Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hofmann
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Druffel-Augustin
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Mogk
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Tyedmers
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Stoecklin
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. Electronic address: bukau@zmbh.uni-heidelberg.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D018869:Heat-Shock Response / Q000235:genetics*; D006706:Homeostasis; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014176:Protein Biosynthesis; D017510:Protein Folding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins