Peroxiredoxin promotes longevity and H<sub>2</sub>O<sub>2</sub>-resistance in yeast through redox-modulation of protein kinase A.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32662770.
- Also identified by DOI 10.7554/eLife.60346 and PMC identifier 7392609.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Peroxiredoxins are H<sub>2</sub>O<sub>2</sub> scavenging enzymes that also carry out H<sub>2</sub>O<sub>2</sub> signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H<sub>2</sub>O<sub>2</sub> and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavenging H<sub>2</sub>O<sub>2</sub>, 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<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub>.
Medical subject headings
- Cyclic AMP-Dependent Protein Kinases
- Hydrogen Peroxide
- Peroxidases
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins