Proteasome β5 subunit overexpression improves proteostasis during aging and extends lifespan in Drosophila melanogaster

Scientific Reports
Nga N NguyenJae H Hur

Abstract

The β5 subunit of the proteasome has been shown in worms and in human cell lines to be regulatory. In these models, β5 overexpression results in upregulation of the entire proteasome complex which is sufficient to increase proteotoxic stress resistance, improve metabolic parameters, and increase longevity. However, fundamental questions remain unanswered, including the temporal requirements for β5 overexpression and whether β5 overexpression can extend lifespan in other species. To determine if adult-only overexpression of the β5 subunit can increase proteasome activity in a different model, we characterized phenotypes associated with β5 overexpression in Drosophila melanogaster adults. We find that adult-only overexpression of the β5 subunit does not result in transcriptional upregulation of the other subunits of the proteasome as they do in nematodes and human cell culture. Despite this lack of a regulatory role, boosting β5 expression increases the chymotrypsin-like activity associated with the proteasome, reduces both the size and number of ubiquitinated protein aggregates in aged flies, and increases longevity. Surprisingly, these phenotypes were not associated with increased resistance to acute proteotoxic insults or impr...Continue Reading

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Citations

Jun 23, 2020·EMBO Reports·Maja C FunkMichael Boutros
Dec 19, 2019·Frontiers in Cell and Developmental Biology·Eleanor R SteadIvana Bjedov
May 28, 2020·International Journal of Molecular Sciences·Jun Hamazaki, Shigeo Murata
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Oct 29, 2020·Genes & Genomics·Garbin Yu, Seogang Hyun
Mar 1, 2021·Redox Biology·Mary Α VasilopoulouNiki Chondrogianni
May 30, 2021·Nature Communications·A RoichmanH Y Cohen

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Methods Mentioned

BETA
protein folding
transgenic
PCR
Protein Assay

Software Mentioned

R
ImageJ
Graphpad Prism
GraphPad
Excel

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