Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A
Journal article, 2020
Peroxiredoxins are H2O2 scavenging enzymes that also carry out H2O2 signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2 and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavenging H2O2, 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 H2O2 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 H2O2 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 H2O2.
chemical biology
S. cerevisiae
peroxiredoxin
glutathionylation
biochemistry
aging
cell biology
protein kinase A
H2O2 signalling
cysteine sulfenylation
Author
F. Roger
University of Gothenburg
Cecilia Picazo Campos
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
W. Reiter
University of Vienna
Marouane Libiad
Centre national de la recherche scientifique (CNRS)
Chikako Asami
University of Gothenburg
Sarah Hanzén
University of Gothenburg
Chunxia Gao
University of Gothenburg
Gilles Lagniel
University Paris-Saclay
Niek Welkenhuysen
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Jean Labarre
University Paris-Saclay
Thomas Nyström
University of Gothenburg
Morten Grötli
University of Gothenburg
Markus Hartl
University of Vienna
M. B. Toledano
Centre national de la recherche scientifique (CNRS)
Mikael Molin
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
University of Gothenburg
eLife
2050084x (eISSN)
Vol. 9 1-32 e60346Subject Categories
Cell Biology
Biochemistry and Molecular Biology
Cell and Molecular Biology
DOI
10.7554/eLife.60346
PubMed
32662770