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
Authors | 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, Lynch, Gordon S., Dodd, Garron T., Watt, Matthew J., Yang, Pengyi, Kiens, Bente, Richter, Erik A. and Parker, Benjamin L. |
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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. |
Keywords | exercises; keletal muscle; phosphoproteomics; AMPK; C18ORF25; signaling |
Year | 2022 |
Journal | Cell Metabolism |
Journal citation | 34, pp. 1561-1577.e9 |
Publisher | Elsevier Inc. |
ISSN | 1550-4131 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.cmet.2022.07.003 |
Scopus EID | 2-s2.0-85136757337 |
Page range | 1561-1577.e9 |
Funder | National 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 | |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
Online | 25 Jul 2022 |
Publication process dates | |
Accepted | 08 Jul 2022 |
Deposited | 05 Dec 2022 |
ARC Funded Research | This output has been funded, wholly or partially, under the Australian Research Council Act 2001 |
Grant ID | 1122376 |
2009642 | |
NNF17OC0027274 | |
NNF18OC0034072 | |
DE220100259 |
https://acuresearchbank.acu.edu.au/item/8y880/phosphoproteomics-of-three-exercise-modalities-identifies-canonical-signaling-and-c180rf25-as-an-ampk-substrate-regulating-skeletal-muscle-function
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