Exercise-induced alterations of myocardial sarcomere dynamics are associated with hypophosphorylation of cardiac troponin I

Bódi, Beáta; Oláh, Attila; Mártha, Lilla; Tóth, Attila; Radovits, Tamás; Merkely, Béla; Papp, Zoltán

doi:10.31083/j.rcm2204119

Cited by 10 publications

(6 citation statements)

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“…Based on our findings of discrepancies between the dynamics of myosin at different temperatures, we wanted to obtain a greater understanding of changes at the protein level during these different hibernating states. The myosin molecule is well-known to be heavily regulated by post-translational modifications (PTMs; Nag et al, 2017 ; Spudich, 2015 ; Bódi et al, 2021 ; Duggal et al, 2014 ; Huang et al, 2015 ; Vandenboom et al, 2013 ; Papadaki et al, 2022 ). We assessed whether hibernation impacts the level of phosphorylation and acetylation on the Myh7 and Myh2 proteins from I. tridecemlineatus .…”

Section: Resultsmentioning

confidence: 99%

Remodeling of skeletal muscle myosin metabolic states in hibernating mammals

Lewis,

Melhedegaard,

Ognjanovic

et al. 2024

eLife

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Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus . We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus , changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20°C). Upon repeating loaded Mant-ATP chase experiments at 8°C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus , which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.

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Section: Resultsmentioning

confidence: 99%

Remodeling of skeletal muscle myosin metabolic states in hibernating mammals

Lewis,

Melhedegaard,

Ognjanovic

et al. 2024

eLife

View full text Add to dashboard Cite

show abstract

“…Based on our findings of discrepancies between the dynamics of myosin at different temperatures, we wanted to obtain a greater understanding of changes at the protein level during these different hibernating states. The myosin molecule is well-known to be heavily regulated by post-translational modifications (PTMs) [28][29][30][31][32][33][34]. We assessed whether hibernation impacts the level of phosphorylation and acetylation on the Myh7 and Myh2 proteins from I. tridecemlineatus.…”

Section: Resultsmentioning

confidence: 99%

Remodelling of skeletal muscle myosin metabolic states in hibernating mammals

Lewis,

Melhedegaard,

Ognjanovic

et al. 2023

Preprint

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Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators,Ictidomys tridecemlineatusandEliomys quercinusand larger hibernators,Ursus arctosandUrsus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure inU. arctosandU. americanusduring hibernation, whilst inI. tridecemlineatusandE. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20°C). Upon repeating loaded Mant-ATP chase experiments at 8°C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor inI. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.

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“…Mechanisms underlying the exercise–induced increase in SRX myosins remain unknown, however, previous studies have demonstrated the importance of post-translational modifications in the regulation of the myosin function (Alamo et al, 2016, Brito et al, 2011, McNamara et al, 2019a, McNamara et al, 2019b). It has been established that exercise can induce vast protein phosphoryla-tion, including that of sarcomeric proteins, and that different training methods can induce distinct training-specific phosphorylation profiles (Needham et al, 2022, Bódi et al, 2021). Further research into the PTMs that specifically occur in endurance-trained individuals could provide insight to why we see this result in EAs and into the mechanisms of control of myosin head conformation.…”

Section: Discussionmentioning

confidence: 99%

Preponderant Myosin Super-Relaxed State In Skeletal Muscle From Endurance Athletes

Lewis

Tabrizian

Nielsen

et al. 2022

Preprint

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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 super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize skeletal muscle metabolism. Indeed, SRX myosins are thought to have a 10-fold reduction in ATP turnover compared to 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 fibres from various athletic and sedentary populations and ran a loaded Mant-ATP chase proto-col. We observed that, in endurance-trained athletes, the amounts of myosin molecules in the SRX state was significantly greater than in age-matched sedentary individuals or than in strength athletes. To further assess whether this change would have an impact on the potency of a SRX-inducing pharmacological compound, Mavacamten, we performed similar analyses as above with and without the drug in muscle fibres from endurance athletes. Surprisingly, we found that 0.3 micromolar of Mavacamten had only marginal effects. Altogether, our results indicate that chronic endurance training-status influences resting skeletal myosin conformations, and Mavacamten potency. Our findings also emphasize that environmental stimuli such as exercise can re-wire the molecular metabolism of human skeletal muscle through myosin.

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Exercise-induced alterations of myocardial sarcomere dynamics are associated with hypophosphorylation of cardiac troponin I

Cited by 10 publications

References 0 publications

Remodeling of skeletal muscle myosin metabolic states in hibernating mammals

Remodeling of skeletal muscle myosin metabolic states in hibernating mammals

Remodelling of skeletal muscle myosin metabolic states in hibernating mammals

Preponderant Myosin Super-Relaxed State In Skeletal Muscle From Endurance Athletes

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