Chemogenetic Mitochondrial H2O2 Generation Triggers Dose-Dependent Skeletal Muscle Wasting Signatures
Meneses-Valdes, R.; Gallero, S.; Hentze, J.; Nielsen, S. F.; Nielsen, J.; Jaimovich, E.; Henriquez-Olguin, C.; Jensen, T. E.
Show abstract
Mitochondrial hydrogen peroxide (mtH2O2) has long been implicated in skeletal muscle atrophy, yet its direct role in vivo has remained unresolved due to methodological constraints. Here, we aimed to establish a chemogenetic platform for precise, compartment-specific induction of mtH2O2 in adult skeletal muscle and to investigate how graded redox stress impacts on muscle proteostasis in vivo. Using mitochondria-targeted D-amino acid oxidase (mtDAAO), we show that prolonged and/or high mtH2O2 exposure progressively activates proteolytic and denervation-associated pathways, culminating in myofiber damage and regeneration. Remarkably, even low exposure to mtH2O2 is sufficient to acutely suppress protein synthesis and induce disuse-like atrophy, without structural damage or overt oxidative stress. This approach provides a powerful in vivo framework to dissect subcellular redox-controlled signaling in muscle and identifies mtH2O2 as a modulator of muscle proteostasis, with therapeutic relevance for muscle-wasting conditions.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms 97%
- Hedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration 96%
- Training-induced bioenergetic improvement in human skeletal muscle is associated with non-stoichiometric changes in the mitochondrial proteome without reorganization of respiratory chain content 96%
Similar papers in this journal
- SOD2 in Skeletal Muscle: New Insights from an Inducible Deletion Model 94%
- Metabolic analysis of sarcopenic muscle identifies positive modulators of longevity and health span in C. elegans 94%
- Multi-Tissue Metabolomics Reveal mtDNA- and Diet-Specific Metabolite Profiles in a Mouse Model of Cardiometabolic Disease 93%
Similar papers in this journal
- Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity. 96%
- Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling 95%
- Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetes patients 94%
Similar papers in this journal
- Immunoresolvents Support Skeletal Myofiber Regeneration via Actions on Myeloid and Muscle Stem Cells 95%
- Fibroblast growth factor-inducible 14 regulates satellite cell self-renewal and expansion during skeletal muscle repair 94%
- Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.