Open AccessSpecific protein homeostatic functions of small heat‐shock proteins increase lifespan
Author(s) -
Vos Michel J.,
Carra Serena,
Ka Bart,
Bosveld Floris,
Klauke Karin,
Sibon Ody C. M.,
Kampinga Harm H.
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12422
Subject(s) - proteostasis , heat shock protein , biology , hsp70 , protein folding , protein aggregation , proteome , microbiology and biotechnology , co chaperone , drosophila melanogaster , longevity , unfolded protein response , biochemistry , genetics , gene , endoplasmic reticulum
Summary 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 ( HSP s). As safeguards of the cellular proteome, HSP s 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 CG 14207 as a novel and potent small HSP member that exclusively assisted in HSP 70‐dependent refolding of stress‐denatured proteins. Furthermore, we report that HSP 67 BC , which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP 70‐independent manner. Importantly, overexpression of both CG 14207 and HSP 67 BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSP s can promote longevity in vivo .