TY - JOUR T1 - Peroxiredoxin promotes longevity and H<sub>2</sub>O<sub>2</sub>-resistance in yeast through redox-modulation of protein kinase A JF - bioRxiv DO - 10.1101/676270 SP - 676270 AU - Friederike Roger AU - Cecilia Picazo AU - Chikako Asami AU - Wolfgang Reiter AU - Sarah Hanzén AU - Chunxia Gao AU - Gilles Lagniel AU - Niek Welkenhuysen AU - Jean Labarre AU - Thomas Nyström AU - Morten Grøtli AU - Markus Hartl AU - Mikael Molin Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/10/01/676270.abstract N2 - Peroxiredoxins are major peroxide scavenging enzymes and mediators of the beneficial effects of caloric restriction on aging. By which mechanism peroxiredoxins stimulate H2O2 resistance and slow down aging is, however, incompletely understood. Here we show that the yeast peroxiredoxin Tsa1 boosts H2O2 tolerance and delays aging not by its action of scavenging H2O2, but by repressing the nutrient signaling protein kinase A (PKA). Tsa1 represses PKA activity through redox modification of the catalytic subunits and a significant proportion of catalytic subunits are glutathionylated on two cysteine residues. Redox modification of the conserved Cys243 in the catalytic subunits 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 responding to H2O2. ER -