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

2050-084X (ISSN)

Vol. 9

Subject Categories

Cell Biology

Biochemistry and Molecular Biology

Cell and Molecular Biology

DOI

10.7554/eLife.60346

PubMed

32662770

More information

Latest update

9/1/2020 1