TY - JOUR

T1 - Physical activity impacts resting skeletal muscle myosin conformation and lowers its ATP consumption

AU - Lewis, Christopher T.A.

AU - Tabrizian, Lee

AU - Nielsen, Joachim

AU - Laitila, Jenni

AU - Beck, Thomas N.

AU - Olsen, Mathilde S.

AU - Ognjanovic, Marija M.

AU - Aagaard, Per

AU - Hokken, Rune

AU - Laugesen, Simon

AU - Ingersen, Arthur

AU - Andersen, Jesper L.

AU - Soendenbroe, Casper

AU - Helge, Jørn W.

AU - Dela, Flemming

AU - Larsen, Steen

AU - Sahl, Ronni E.

AU - Rømer, Tue

AU - Hansen, Mikkel T.

AU - Frandsen, Jacob

AU - Suetta, Charlotte

AU - Ochala, Julien

N1 - Publisher Copyright: © 2023 Lewis et al.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85160456042&partnerID=8YFLogxK

U2 - 10.1085/jgp.202213268

DO - 10.1085/jgp.202213268

M3 - Journal article

C2 - 37227464

AN - SCOPUS:85160456042

VL - 155

JO - Journal of General Physiology

JF - Journal of General Physiology

SN - 0022-1295

IS - 7

M1 - e202213268

ER -