Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function

R Blazev; CS Carl; YK Ng; J Molendijk; CT Voldstedlund; Y Zhao; D Xiao; AJ Kueh; PM Miotto; VR Haynes; JP Hardee; JD Chung; JW McNamara; H Qian; P Gregorevic; JS Oakhill; MJ Herold; TE Jensen; L Lisowski; GS Lynch; GT Dodd; MJ Watt; P Yang; B Kiens; EA Richter; BL Parker

Journal article

Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function

R Blazev, CS Carl, YK Ng, J Molendijk, CT Voldstedlund, Y Zhao, D Xiao, AJ Kueh, PM Miotto, VR Haynes, JP Hardee, JD Chung, JW McNamara, H Qian, P Gregorevic, JS Oakhill, MJ Herold, TE Jensen, L Lisowski, GS Lynch Show all

Cell Metabolism | CELL PRESS | Published : 2022

DOI: 10.1016/j.cmet.2022.07.003

Abstract

Exercise induces signaling networks to improve muscle function and confer health benefits. To identify divergent and common signaling networks during and after different exercise modalities, we performed a phosphoproteomic analysis of human skeletal muscle from a cross-over intervention of endurance, sprint, and resistance exercise. This identified 5,486 phosphosites regulated during or after at least one type of exercise modality and only 420 core phosphosites common to all exercise. One of these core phosphosites was S67 on the uncharacterized protein C18ORF25, which we validated as an AMPK substrate. Mice lacking C18ORF25 have reduced skeletal muscle fiber size, exercise capacity, and mus..

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University of Melbourne Researchers

Ronnie Blazev Author

Paula Miotto Author

Hongwei Qian Author

Paul Gregorevic Author

Related Projects (1)

SKELETAL MUSCLE SIGNAL TRANSDUCTION RELATED TO EXERCISE, METABOLIC DISEASE AND HUMAN HEALTH

Exercise is one of the best prevention and treatment strategies for all major human diseases. Despite these well documented advantages, we s..

Grants

Awarded by Australian Government

Funding Acknowledgements

We thank Nicholas Williamson, Ching-Seng Ang, Shuai Nie, Swati Varshney, and Michael Leeming for instrument support in the Bio21 Mass Spectrometry and Proteomics Facility. This research was supported by access to the Melbourne Mouse Metabolic Phenotyping Platform at the University of Melbourne. This work was funded by an Australian National Health and Medical Research Council (NHMRC) project grant (APP1122376), a Diabetes Australia grant, a University of Melbourne Driving Research Momentum Grant, and an NHMRC Emerging Leader Investigator Grant (APP2009642) to B.L.P., and by grants from the Novo Nordisk Foundation (NNF17OC0027274 and NNF18OC0034072) to E.A.R. J.P.H. was supported by a McKenzie Research Fellowship from the University of Melbourne and an Australian Research Council Discovery Early Career Award (DE220100259). P.M.M. was supported by the Natural Sciences and Engineering Research Council of Canada and Canadian Institutes of Health Research. The generation of C18ORF25 KO mice was supported by Phenomics Australia and the Australian Government through the National Collaborative Research Infrastructure Strategy program.