title: Specific protein homeostatic functions of small heat-shock proteins increase lifespan.
abstract: During aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat-shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress-denatured substrates and/or to prevent aggregation of disease-associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70-dependent refolding of stress-denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70-independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo.
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Vos
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Serena
authors.initials: S
authors.lastname: Carra
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Kanon
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Bosveld
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Klauke
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ody C M
authors.initials: OC
authors.lastname: Sibon
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Harm H
authors.initials: HH
authors.lastname: Kampinga
mesh_terms: D000818:Animals; D004330:Drosophila; D005260:Female; D050888:Heat-Shock Proteins, Small / Q000502:physiology*; D006706:Homeostasis; D008136:Longevity / Q000502:physiology*; D008297:Male
chemical_list: D050888:Heat-Shock Proteins, Small
keywords: Drosophila melanogaster; HSPB family; aging; longevity; protein homeostasis; small heat-shock protein