Biology subjects

Casas-Martinez, J. C.

Publications and source records attributed to Casas-Martinez, J. C..

3 recordsLinked to original sources

bioRxiv2025

PERK orchestrates MERCS formation and mitochondrial remodelling promoting physiological adaptations during adaptive UPR signalling

The transfer of information and metabolites between mitochondria and the ER is mediated by mitochondria-ER contact sites (MERCS), facilitating adaptations following changes in cellular homeostasis. MERCS are dynamic structures, essential for maintaining cellular homeostasis through modulation of calcium transfer, redox signalling, lipid transfer, autophagy and mitochondrial dynamics. Acute ER stress in myoblasts promoted myogenesis that required the PERK arm of the UPRER for increased MERCS assembly, mitochondrial turnover and function. Similarly, induction of acute UPRER during early development in C. elegans resulted in increased lifespan and healthspan. Adaptive UPRER signalling in myoblasts and C. elegans, increased MERCS assembly and activated autophagy, ultimately promoting mitochondrial remodelling. Adaptations were dependent on the developmental stage, as treatment of myotubes or adult C. elegans resulted in a maladaptive response. The results identify that PERK is required for increased mitochondrial ER communication in response to adaptive UPR signalling, promoting mitochondrial remodelling and improved physiological function. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/633960v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@66c0f2org.highwire.dtl.DTLVardef@57814org.highwire.dtl.DTLVardef@10e87d5org.highwire.dtl.DTLVardef@f7b69e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

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

molecular biology↗

bioRxiv2022

Peroxiredoxin 2 is required for the redox mediated adaptation to exercise

Exercise generates a site-specific increase in Reactive Oxygen Species (ROS) within muscle required for a beneficial adaptive response by activation of specific signalling pathways. Here, we demonstrate that Peroxiredoxin 2 (Prdx2), an abundant cytoplasmic 2-Cys peroxiredoxin, is required for the adaptive beneficial hormesis response to H2O2. A short bolus addition of H2O2 increases mitochondrial capacity and improves myogenesis of cultured myoblasts, this beneficial adaptive response was suppressed in myoblasts with decreased expression of cytoplasmic Prdxs. A swimming exercise protocol in C. elegans increased mitochondrial content, fitness, survival and longevity in wild type (N2) worms. In contrast, prdx-2 mutant worms had decreased fitness, disrupted mitochondria, reduced survival and lifespan following exercise. Global proteomics following exercise identified distinct changes in the proteome of N2 and prdx-2 mutants. Furthermore, a redox proteomic approach to quantify reversible oxidation of individual Cysteine residues revealed a relatively more oxidised redox state following exercise in the prdx-2 mutants. Our results demonstrate that conserved cytoplasmic 2-Cys Peroxiredoxins are required for the beneficial adaptive response to a physiological stress.

molecular biology↗