Peroxiredoxin 2 Regulates DAF-16/FOXO Mediated Mitochondrial Remodelling in Response to Exercise that is Disrupted in Ageing

Ageing is associated with mitochondrial dysfunction and increased oxidative stress. Exercise generates endogenous reactive oxygen species (ROS) and promotes rapid mitochondrial remodelling. We investigated the role of Peroxiredoxin 2 (PRDX-2) in mitochondrial adaptations to exercise and ageing using Caenorhabditis elegans as a model system. PRDX-2 was required for the mitochondrial remodelling in response to exercise mediated by DAF-16 nuclear localisation. Employing an acute exercise and recovery cycle, we demonstrated exercise-induced mitochondrial ER contact sites (MERCS) assembly and mitochondrial remodelling dependent on PRDX-2 and DAF-16 signalling. There was increased mitochondrial fragmentation, elevated ROS and an altered redox state of PRDX-2, concomitant with impaired DAF-16 nuclear localisation during ageing. Similarly, the prdx-2 mutant strain exhibited increased mitochondrial fragmentation and a failure to activate DAF-16 required for mitochondrial fusion. Collectively, our data highlight the critical role of PRDX-2 in orchestrating mitochondrial remodelling in response to a physiological stress by regulating DAF-16 nuclear localisation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/593975v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@50b94forg.highwire.dtl.DTLVardef@1b62d31org.highwire.dtl.DTLVardef@1511d0eorg.highwire.dtl.DTLVardef@4a9b6d_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIExercise generates ROS and promotes mitochondrial remodelling dependent on DAF-16. C_LIO_LIExercise induces mitochondrial ER contact site assembly and mitochondrial dynamics. C_LIO_LIAgeing and loss of PRDX-2 results in disrupted mitochondrial fusion. C_LIO_LIThe redox state of PRDX-2 determines appropriate DAF-16 nuclear localisation. C_LI