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 -