Peroxiredoxin 2 is required for the exercise induced redox mediated adaptation to exercise

ABSTRACT: During exercise there is a site-specific increase in ROS within muscle required for the beneficial adaptive response by activation of specific signalling pathways. Peroxiredoxin 2 (Prdx2), an abundant cytoplasmic 2-Cys peroxidase, is required for the adaptive beneficial hormesis response to H2O2, myoblasts with knockdown of Prdx2 did not increase mitochondrial content and had disrupted myogenesis. Using a 5-day swimming protocol in C. elegans, previously been demonstrated to improve healthspan, we observed increased mitochondrial content, fitness, survival and longevity in wild type (N2) worms. However, prdx-2 mutant worms had decreased fitness, disrupted mitochondria, reduced survival and lifespan following exercise. Global proteomics following exercise revealed an increase in the abundance of proteins involved in fatty oxidation and ion transport, decrease in proteins involved in cuticle formation in N2 worms. In the prdx-2 mutants following exercise there was an increase in proteins related to the mTOR pathway and decrease in transsulfuration and microRNA biogenesis proteins. Relative quantification of the reversible oxidation state of individual Cysteine (Cys) residues revealed an increased oxidation of specific Cys residues following exercise in prdx-2 mutant. A number of regulatory Cys residues of metabolic, cytoskeletal and calcium handling proteins are reduced in N2 worms. A redox signalling relay whereby the oxidative equivalents from ROS are transferred from evolutionary conserved Prdxs to target proteins, would confer specificity on redox signalling required for the beneficial adaptations to exercise.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: Eduardo Zarzuela  

LAB HEAD: Javier Muñoz Peralta

PROVIDER: PXD037698 | Pride | 2023-03-11

REPOSITORIES: Pride