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Updated: Mar 28, 2026

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Specific protein homeostatic functions of small heat-shock proteins increase lifespan
Michel J Vos1, Serena Carra1, Bart Kanon1
1Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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.
Insights
Cellular protein damage increases with age. This study identifies two small heat-shock proteins (HSPs) in Drosophila that combat protein aggregation and misfolding, extending lifespan.
Area of Science:
- Cellular Biology
- Aging Research
- Protein Homeostasis
Background:
- Aging leads to accumulation of damaged proteins, impairing cellular function.
- Protein quality control networks, especially heat-shock proteins (HSPs), mitigate protein damage.
- Small HSPs play diverse roles in maintaining proteome integrity.
Purpose of the Study:
- To compare the functional capacities of all Drosophila melanogaster small HSP family members.
- To investigate their roles in refolding stress-denatured proteins and preventing aggregation of disease-associated proteins.
- To assess the impact of small HSPs on lifespan in vivo.
Main Methods:
- Comparative analysis of small heat-shock protein (HSP) family members in Drosophila melanogaster.
- Assays to evaluate substrate refolding and prevention of protein aggregation.
- In vivo studies involving overexpression of specific small HSPs in Drosophila.
Main Results:
- CG14207 was identified as a novel small HSP that aids in HSP70-dependent refolding of denatured proteins.
- HSP67BC demonstrated potent, HSP70-independent prevention of toxic protein aggregation.
- Overexpression of CG14207 and HSP67BC in Drosophila resulted in a modest lifespan extension.
Conclusions:
- Functionally distinct small HSPs contribute to cellular proteostasis.
- Targeted enhancement of specific small HSPs can ameliorate protein aggregation and extend lifespan.
- Small HSPs represent potential therapeutic targets for age-related proteinopathies.
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