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bioRxiv · 10.1101/2024.05.13.593975

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

Xia, Q.·Li, P.·Casas-Martinez, J. C.·Miranda-Vizuete, A.·McDermott, E.·Dockery, P.·Goljanek-Whysall, K.·McDonagh, B.
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Abstract

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

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Xia, Q., Li, P., Casas-Martinez, J. C., Miranda-Vizuete, A., McDermott, E., Dockery, P., Goljanek-Whysall, K., McDonagh, B.. 2024-05-13. Peroxiredoxin 2 Regulates DAF-16/FOXO Mediated Mitochondrial Remodelling in Response to Exercise that is Disrupted in Ageing. https://doi.org/10.1101/2024.05.13.593975

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