Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A
Artikel i vetenskaplig tidskrift, 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

Författare

F. Roger

Göteborgs universitet

Cecilia Picazo Campos

Chalmers, Biologi och bioteknik, Systembiologi

W. Reiter

Universität Wien

Marouane Libiad

Centre national de la recherche scientifique (CNRS)

Chikako Asami

Göteborgs universitet

Sarah Hanzén

Göteborgs universitet

Chunxia Gao

Göteborgs universitet

Gilles Lagniel

Université Paris-Saclay

Niek Welkenhuysen

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Jean Labarre

Université Paris-Saclay

Thomas Nyström

Göteborgs universitet

Morten Grötli

Göteborgs universitet

Markus Hartl

Universität Wien

M. B. Toledano

Centre national de la recherche scientifique (CNRS)

Mikael Molin

Chalmers, Biologi och bioteknik, Systembiologi

Göteborgs universitet

eLife

2050-084X (ISSN)

Vol. 9

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Cell- och molekylärbiologi

DOI

10.7554/eLife.60346

PubMed

32662770

Mer information

Senast uppdaterat

2020-09-01