Turning over new ideas in human skeletal muscle proteostasis: what do we know and where to from here?

Lim, Changhyun ORCID: https://orcid.org/0000-0002-5437-8063, McKendry, James, Lees, Matthew, Atherton, Philip J. ORCID: https://orcid.org/0000-0002-7286-046X, Burd, Nicholas A., Holwerda, Andrew M., van Loon, Luc J. C., McGlory, Chris, Mitchell, Cameron J., Smith, Kenneth, Wilkinson, Daniel J., Stokes, Tanner and Phillips, Stuart M. ORCID: https://orcid.org/0000-0002-1956-4098 (2025) Turning over new ideas in human skeletal muscle proteostasis: what do we know and where to from here? Experimental Physiology. ISSN 0958-0670

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Abstract

Understanding the turnover of proteins in tissues gives information as to how external stimuli result in phenotypic change. Nowhere is such phenotypic change more conspicuous than skeletal muscle, which can be effectively remodelled by increased loading, ageing and unloading (disuse), all of which are subject to modification by nutrition and other environmental stimuli. The understanding of muscle proteome remodelling has undergone a renaissance recently with the reintroduction of deuterated water (D2O) and its ingestion to label amino acids and measure their incorporation into proteins. However, there is confusion around the use of the deuterated water methodology and the interpretation of the data it provides. Here, we provide a short review of some of the more salient features of the method and clarify some of the confusion around the method of deuterated water methods and its use in humans and how the interpretation of the data is in contrast to that of rodents.