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ABSTRACT: Reactive oxygen species (ROS) regulate protein function through reversible cysteine oxidation. In human skeletal muscle, exercise-induced ROS initiates adaptations such as mitochondrial biogenesis, increased insulin sensitivity, and hypertrophy. However, specific protein targets of ROS regulation during exercise remain unclear owing to longstanding challenges in analyzing redox proteomes in vivo. We applied cysteine derivatization and multiplexed proteomics to map muscle protein cysteine oxidation in humans during exercise. The OxiMuscle dataset quantifies reversible modifications across 17,492 cysteine sites in young men undergoing three types of exercise, providing the first comprehensive analysis of the exercise-regulated redox cysteine proteome in humans. We systematically define cysteine oxidation targets regulated by at least one form of exercise, many of which reside in proteins with established roles in muscle physiology. Among these sites is a redox-regulated cysteine on the autophagy receptor protein p62. We demonstrate that reversible oxidation of this cysteine regulates p62-mediated autophagy upon myotube contraction and mouse muscle adaptation to exercise in vivo. Together, these results unveil a redox-driven mechanism involved in exercise-induced autophagy and muscle adaptation.
Guide to exploring Oximuscle
-Select the exercise type you would like to explore.
-Add the UniProt name for your favorite protein to see all cysteine sites mapped for that protein.
-If your protein is not found, likely it was not mapped in the selected dataset. Please ensure you have entered the correct UniProt name and exercise type.
-Cysteine data for individual proteins can be downloaded from the search window.
-The entire dataset can be downloaded from the Download tab.
Note the cysteine site numbers indicate the cysteine(s) that were labeled for a given peptide.
The web application was developed by Shelley Wei, Yu Lei, and Jonathan Petrocelli (Chouchani Lab, DFCI/HMS).
Enter your search query:
Search for a cysteine site
Summary Table
Median % Oxidation
Delta % Oxidation from Pre
Mapped Cysteine Position
Human
Protein Sequence
Human
External Resources
Bulk Download Data Files
Download flat files (comma-separated) containing all data displayed in the Oximuscle website.
Download All Cysteine Data
Download Endurance All Sites
Download Sprint All Sites
Download Resistance All Sites
Download All Sites Ranked
Acknowledgements
The Oximuscle website uses the following libraries and tools:
• InnateDB: systems biology of the innate immune response database https://www.innatedb.com/
• Uniprot: https://www.uniprot.org/
• Oximouse dataset: https://oximouse.hms.harvard.edu/
• PDB protein data bank: https://www.rcsb.org/
• AlphaFold protein structure database: https://alphafold.ebi.ac.uk/
• DEPOD human DEPhOsphorylation database: https://depod.bioss.uni-freiburg.de
• KinaseMD: Kinase mutations and drug response database: https://bioinfo.uth.edu/kmd/index.html
• Human Protein Atlas: https://www.proteinatlas.org/
• TFLink database: https://tflink.net
• Mammalian metabolic enzyme database: https://esbl.nhlbi.nih.gov/Databases/KSBP2/Targets/Lists/MetabolicEnzymes/MetabolicEnzymeDatabase.html
• Shiny: https://shiny.posit.co
Copyright and License Information
The Oximuscle website was developed and is licensed under the Creative Commons Attribution-ShareAlike 4.0 International License.
Images presented and generated on the Oximuscle website are licensed under the Creative Commons Attribution-ShareAlike 4.0 International License.