Specific protein homeostatic functions of small heat-shock proteins increase lifespan

Michel J. Vos, Serena Carra, Bart Kanon, Floris Bosveld, Karin Klauke, Ody C. M. Sibon, Harm H. Kampinga*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)
258 Downloads (Pure)

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 invivo.

Original languageEnglish
Pages (from-to)217-226
Number of pages10
JournalAging Cell
Volume15
Issue number2
DOIs
Publication statusPublished - Apr-2016

Keywords

  • protein homeostasis
  • longevity
  • aging
  • Drosophila melanogaster
  • small heat-shock protein
  • HSPB family
  • DROSOPHILA-MELANOGASTER
  • MOLECULAR CHAPERONES
  • GENE-EXPRESSION
  • GENOME-WIDE
  • IN-VIVO
  • POLYGLUTAMINE AGGREGATION
  • CAENORHABDITIS-ELEGANS
  • HUNTINGTONS-DISEASE
  • OXIDATIVE STRESS
  • MAMMALIAN-CELLS

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