Regulatory mechanisms of skeletal muscle protein turnover during exercise

Rose AJ, Richter EA. Regulatory mechanisms of skeletal muscle protein turnover during exercise. J Appl Physiol 106: 1702-1711, 2009. First published Janaury 29, 2009; doi: 10.1152/japplphysiol.91375.2008.-Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding, fasting, and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regard to protein turnover, there are now consistent data from tracer studies in rodents and humans showing that global protein synthesis is blunted in working skeletal muscle. Whether there is altered skeletal muscle protein breakdown during exercise remains unclear. The blunting of protein synthesis is believed to be mediated by suppressed mRNA translation initiation and elongation steps involving, but not limited to, changes in eukaryotic initiation factor 4E binding protein 1 and eukaryotic elongation factor 2 phosphorylation (eEF2), respectively. Evidence is provided that upstream signaling to translation factors is mediated by signaling downstream of changes in intracellular Ca2+ and energy turnover. In particular, a signaling cascade involving Ca2+/calmodulin-eEF2 kinase-eEF2 is implicated. The possible functional significance of altered protein turnover in working skeletal muscle during exercise is discussed. Further work with available and new techniques will undoubtedly reveal the functional significance and signaling mechanisms behind changes in skeletal muscle protein turnover during exercise.