Peroxiredoxin promotes longevity and H 2 O 2 -resistance in yeast through redox-modulation of protein kinase A

Peroxiredoxins are H O scavenging enzymes that also carry out H O signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H O and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions...

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Published ineLife Vol. 9
Main Authors Roger, Friederike, Picazo, Cecilia, Reiter, Wolfgang, Libiad, Marouane, Asami, Chikako, Hanzén, Sarah, Gao, Chunxia, Lagniel, Gilles, Welkenhuysen, Niek, Labarre, Jean, Nyström, Thomas, Grøtli, Morten, Hartl, Markus, Toledano, Michel B, Molin, Mikael
Format Journal Article
LanguageEnglish
Published England 14.07.2020
Subjects
Cyclic AMP-Dependent Protein Kinases - metabolism
Hydrogen Peroxide - metabolism
Longevity
Oxidation-Reduction
Peroxidases - genetics
Peroxidases - metabolism
Saccharomyces cerevisiae - enzymology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
peroxiredoxin
cell biology
chemical biology
glutathionylation
biochemistry
aging
cysteine sulfenylation
protein kinase A
H2O2 signalling
S. cerevisiae
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Summary:Peroxiredoxins are H O scavenging enzymes that also carry out H O signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H O and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavenging H O , but by repressing the nutrient signaling Ras-cAMP-PKA pathway at the level of the protein kinase A (PKA) enzyme. Tsa1 stimulates sulfenylation of cysteines in the PKA catalytic subunit by H O and a significant proportion of the catalytic subunits are glutathionylated on two cysteine residues. Redox modification of the conserved Cys243 inhibits the phosphorylation of a conserved Thr241 in the kinase activation loop and enzyme activity, and preventing Thr241 phosphorylation can overcome the H O sensitivity of Tsa1-deficient cells. Results support a model of aging where nutrient signaling pathways constitute hubs integrating information from multiple aging-related conduits, including a peroxiredoxin-dependent response to H O .
ISSN:2050-084X