High intensity interval training remodels the proteome and acetylome in human skeletal muscle

Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations in the skeletal muscle proteome, including post-translational modifications, regulate its metabolic adaptations to exercise. Here, we examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal muscle, revealing the response of 3168 proteins and 1263 lysine acetyl-sites on 464 acetylated proteins. We identified novel protein adaptations to exercise training involved in metabolism and excitation-contraction coupling. Furthermore, HIIT increased the acetylation of mitochondrial proteins, particularly those of complex V, likely via non-enzymatic mechanisms. We also highlight the regulation of novel exercise-responsive histone acetyl-sites. These data demonstrate the plasticity of the skeletal muscle proteome and acetylome, providing insight into the regulation of contractile, metabolic and transcriptional processes within skeletal muscle. Herein, we provide a substantial hypothesis-generating resource to stimulate further mechanistic research investigating how exercise improves metabolic health.