Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in replicative lifespan extension

Campion, Richard, Bloxam, Leanne, Burrow, Kimberley, Brownridge, Philip J, Pentland, Daniel R, Thomas, Patricia, Gourlay, Campbell W, Eyers, Claire E ORCID: 0000-0002-3223-5926, Barclay, Jeff W and Morgan, Alan ORCID: 0000-0002-0346-1289
(2021) Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in replicative lifespan extension. BIOCHEMICAL JOURNAL, 478 (24). pp. 4153-4167.

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Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms. However, the downstream effector proteins that ultimately mediate lifespan extension are less clear. To shed light on this, we used a proteomic approach on budding yeast. Our reasoning was that analysis of proteome-wide changes in response to DR might enable the identification of proteins that mediate its physiological effects, including replicative lifespan extension. Of over 2500 proteins we identified by liquid chromatography-mass spectrometry, 183 were significantly altered in expression by at least 3-fold in response to DR. Most of these proteins were mitochondrial and/or had clear links to respiration and metabolism. Indeed, direct analysis of oxygen consumption confirmed that mitochondrial respiration was increased several-fold in response to DR. In addition, several key proteins involved in mating, including Ste2 and Ste6, were down-regulated by DR. Consistent with this, shmoo formation in response to α-factor pheromone was reduced by DR, thus confirming the inhibitory effect of DR on yeast mating. Finally, we found that Hsp26, a member of the conserved small heat shock protein (sHSP) family, was up-regulated by DR and that overexpression of Hsp26 extended yeast replicative lifespan. As overexpression of sHSPs in Caenorhabditis elegans and Drosophila has previously been shown to extend lifespan, our data on yeast Hsp26 suggest that sHSPs may be universally conserved effectors of longevity.

Item Type: Article
Uncontrolled Keywords: Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Heat-Shock Proteins, Proteome
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 08 Nov 2021 11:04
Last Modified: 18 Jan 2023 21:25
DOI: 10.1042/BCJ20210432
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