title: Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress.
abstract: Heat causes protein misfolding and aggregation and, in eukaryotic cells, triggers aggregation of proteins and RNA into stress granules. We have carried out extensive proteomic studies to quantify heat-triggered aggregation and subsequent disaggregation in budding yeast, identifying >170 endogenous proteins aggregating within minutes of heat shock in multiple subcellular compartments. We demonstrate that these aggregated proteins are not misfolded and destined for degradation. Stable-isotope labeling reveals that even severely aggregated endogenous proteins are disaggregated without degradation during recovery from shock, contrasting with the rapid degradation observed for many exogenous thermolabile proteins. Although aggregation likely inactivates many cellular proteins, in the case of a heterotrimeric aminoacyl-tRNA synthetase complex, the aggregated proteins remain active with unaltered fidelity. We propose that most heat-induced aggregation of mature proteins reflects the operation of an adaptive, autoregulatory process of functionally significant aggregate assembly and disassembly that aids cellular adaptation to thermal stress.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Edward W J
authors.initials: EW
authors.lastname: Wallace
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Kear-Scott
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Pilipenko
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Schwartz
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Pawel R
authors.initials: PR
authors.lastname: Laskowski
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Rojek
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Katanski
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Riback
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Dion
authors.affiliation: Department of Statistics, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Franks
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA; Department of Statistics, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Edoardo M
authors.initials: EM
authors.lastname: Airoldi
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Pan
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Budnik
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA. Electronic address: dadrummond@uchicago.edu.
authors.forename: D Allan
authors.initials: DA
authors.lastname: Drummond
mesh_terms: D003513:Cycloheximide / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D018869:Heat-Shock Response; D066329:Protein Aggregates; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D066329:Protein Aggregates; D011500:Protein Synthesis Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D003513:Cycloheximide