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Review
. 2025 Jul 2;3(1):30.
doi: 10.1038/s44324-025-00073-2.

Skeletal muscle proteomics: considerations and opportunities

Julian P H Wong  1 , Yaan-Kit Ng  1 , Jeppe Kjærgaard  2 , Ronnie Blazev  1 , Atul S Deshmukh  2 , Benjamin L Parker  3
Affiliations
Review

Skeletal muscle proteomics: considerations and opportunities

Julian P H Wong et al. NPJ Metab Health Dis. .

Abstract

Skeletal muscle accounts for 30-40% of body weight and plays an indispensable role in maintaining movement and is also a central regulator of whole-body metabolism. As such, understanding the molecular mechanisms of skeletal muscle health and disease is vital. Proteomics has been revolutionized in recent years and provided new insights into skeletal muscle. In this review, we first highlight important considerations unique to the field which make skeletal muscle one of the most challenging tissues to analyse by mass spectrometry. We then highlight recent advances using the latest case studies and how this has allowed coverage of the skeletal muscle temporal, fibre type and stem cells proteome. We also discuss how exercise and metabolic dysfunction can remodel the muscle proteome. Finally, we discuss the future directions of the field and how they can be best leveraged to increase understanding of human biology.

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Conflict of interest statement

Competing interests: B.L.P. is an editor of npj Metabolic Health and Disease. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Characteristics of analysing the skeletal muscle proteome by mass spectrometry.
A Relative intensity of the top 100 most abundant proteins in various mouse tissues. B Number of theoretical tryptic peptides generated from top 10 most abundant proteins in various mouse tissues. C Number of observed tryptic peptides in mouse skeletal muscle and heart. Figure (A) adapted from. C adapted from,.
Fig. 2
Fig. 2. Comparison of the proteomic analysis of whole cell lysate verses biochemical subcellular fractionation.
A Total protein stain by SyproRuby of mouse skeletal muscle whole cell lysate (WCL) and four subcellular fractions. B Number of proteins identified in WCL and subcellular fractions by single shot LC-MS/MS with DIA. C Coefficient of variation of the proteins identified in all 3 technical replicates of the WCL and subcellular fractions.
See this image and copyright information in PMC

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