It has recently been established that myosin, the molecular motor protein, is able to exist in two conformations in relaxed skeletal muscle. These conformations are known as the super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize ATP consumption and skeletal muscle metabolism. Indeed, SRX myosins are thought to have a 5- to 10-fold reduction in ATP turnover compared with DRX myosins. Here, we investigated whether chronic physical activity in humans would be associated with changes in the proportions of SRX and DRX skeletal myosins. For that, we isolated muscle fibers from young men of various physical activity levels (sedentary, moderately physically active, endurance-trained, and strength-trained athletes) and ran a loaded Mant-ATP chase protocol. We observed that in moderately physically active individuals, the amount of myosin molecules in the SRX state in type II muscle fibers was significantly greater than in age-matched sedentary individuals. In parallel, we did not find any difference in the proportions of SRX and DRX myosins in myofibers between highly endurance- and strength-trained athletes. We did however observe changes in their ATP turnover time. Altogether, these results indicate that physical activity level and training type can influence the resting skeletal muscle myosin dynamics. Our findings also emphasize that environmental stimuli such as exercise have the potential to rewire the molecular metabolism of human skeletal muscle through myosin.
Physical activity impacts resting skeletal muscle myosin conformation and lowers its ATP consumption
Disclosures: L. Tabrizian, C. Lewis, and J. Ochala reported grants from Carlsberg Foundation Grant (CF20-0113) during the conduct of the study. No other disclosures were reported.
This work is part of a special issue on Myofilament Function 2022.
- Award Id(s): CF20-0113
Christopher T.A. Lewis, Lee Tabrizian, Joachim Nielsen, Jenni Laitila, Thomas N. Beck, Mathilde S. Olsen, Marija M. Ognjanovic, Per Aagaard, Rune Hokken, Simon Laugesen, Arthur Ingersen, Jesper L. Andersen, Casper Soendenbroe, Jørn W. Helge, Flemming Dela, Steen Larsen, Ronni E. Sahl, Tue Rømer, Mikkel T. Hansen, Jacob Frandsen, Charlotte Suetta, Julien Ochala; Physical activity impacts resting skeletal muscle myosin conformation and lowers its ATP consumption. J Gen Physiol 3 July 2023; 155 (7): e202213268. doi: https://doi.org/10.1085/jgp.202213268
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