Phosphoproteomics of three exercise modalities identifies canonical signaling and C180RF25 as an AMPK substrate regulating skeletal muscle function

Journal article


Blazev, Ronnie, Carl, Christian S., Ng, Yaan-Kit, Molendijk, Jeffrey, Voldstedlund, Christian T., Zhao, Yuanyuan, Xiao, Di, Kueh, Andrew J., Miotto, Paula M., Haynes, Vanessa R., Hardee, Justin P., Chung, Jin D., MacNamara, James W., Qian, Hongwei, Gregorevic, Paul, Oakhill, Jonathan S., Herold, Marco J., Jensen, Thomas E., Lisowski, Leszek, ... Parker, Benjamin L.. (2022). Phosphoproteomics of three exercise modalities identifies canonical signaling and C180RF25 as an AMPK substrate regulating skeletal muscle function. Cell Metabolism. 34, pp. 1561-1577.e9. https://doi.org/10.1016/j.cmet.2022.07.003
AuthorsBlazev, Ronnie, Carl, Christian S., Ng, Yaan-Kit, Molendijk, Jeffrey, Voldstedlund, Christian T., Zhao, Yuanyuan, Xiao, Di, Kueh, Andrew J., Miotto, Paula M., Haynes, Vanessa R., Hardee, Justin P., Chung, Jin D., MacNamara, James W., Qian, Hongwei, Gregorevic, Paul, Oakhill, Jonathan S., Herold, Marco J., Jensen, Thomas E., Lisowski, Leszek, Lynch, Gordon S., Dodd, Garron T., Watt, Matthew J., Yang, Pengyi, Kiens, Bente, Richter, Erik A. and Parker, Benjamin L.
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 muscle contractile function, and this was associated with reduced phosphorylation of contractile and Ca2+ handling proteins. Expression of C18ORF25 S66/67D phospho-mimetic reversed the decreased muscle force production. This work defines the divergent and canonical exercise phosphoproteome across different modalities and identifies C18ORF25 as a regulator of exercise signaling and muscle function.

Keywordsexercises; keletal muscle; phosphoproteomics; AMPK; C18ORF25; signaling
Year2022
JournalCell Metabolism
Journal citation34, pp. 1561-1577.e9
PublisherElsevier Inc.
ISSN1550-4131
Digital Object Identifier (DOI)https://doi.org/10.1016/j.cmet.2022.07.003
Scopus EID2-s2.0-85136757337
Page range1561-1577.e9
FunderNational Health and Medical Research Council (NHMRC)
Diabetes Australia
University of Melbourne
Novo Nordisk Foundation
Australian Research Council (ARC)
Natural Sciences and Engineering Research Council of Canada (NSERC)
Canadian Institutes of Health Research
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All rights reserved
File Access Level
Controlled
Output statusPublished
Publication dates
Online25 Jul 2022
Publication process dates
Accepted08 Jul 2022
Deposited05 Dec 2022
ARC Funded ResearchThis output has been funded, wholly or partially, under the Australian Research Council Act 2001
Grant ID1122376
2009642
NNF17OC0027274
NNF18OC0034072
DE220100259
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