The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle

Cooke, Roger

doi:10.1007/s12551-011-0044-9

Cited by 104 publications

(147 citation statements)

References 100 publications

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“…The pioneering work of Cooke and coworkers proposed a new myosin state, that they called super-relaxed state (SRX) which exhibits a slow ATP turnover rate as a mechanism in thermogenesis in resting skeletal (Stewart et al 2010;Cooke 2011;McNamara et al 2015). In tarantula muscle, there is an additional very slow ATP turnover rate (Naber et al 2011;Wilson et al 2014).…”

Section: Super-relaxation (Srx)mentioning

confidence: 99%

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function

et al. 2017

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The tarantula skeletal muscle X-ray diffraction pattern suggested that the myosin heads were helically arranged on the thick filaments. Electron microscopy (EM) of negatively stained relaxed tarantula thick filaments revealed four helices of heads allowing a helical 3D reconstruction. Due to its low resolution (5.0 nm), the unambiguous interpretation of densities of both heads was not possible. A resolution increase up to 2.5 nm, achieved by cryo-EM of frozen-hydrated relaxed thick filaments and an iterative helical real space reconstruction, allowed the resolving of both heads. The two heads, Bfree^and Bblocked^, formed an asymmetric structure named the Binteracting-heads motif^(IHM) which explained relaxation by self-inhibition of both heads ATPases. This finding made tarantula an exemplar system for thick filament structure and function studies. Heads were shown to be released and disordered by Ca 2+ -activation through myosin regulatory light chain phosphorylation, leading to EM, small angle X-ray diffraction and scattering, and spectroscopic and biochemical studies of the IHM structure and function. The results from these studies have consequent implications for understanding and explaining myosin super-relaxed state and thick filament activation and regulation. A cooperative phosphorylation mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 mono-phosphorylated free heads, explains super-relaxation, force potentiation and posttetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction.

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Section: Super-relaxation (Srx)mentioning

confidence: 99%

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function

et al. 2017

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“…As strenuous activity was limited in some of these protocols, the diversity of weight gain was attributed to light activities, such as fidgeting (3,4). Alternatively, the diversity may be due to variation in the metabolic rate of resting muscle and to how this responds to activity (5).…”

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confidence: 99%

“…The metabolic rate of resting, living skeletal muscle is variable, responding to a number of factors, including the hormones leptin and epinephrine (for review, see ref. 5). Although the resting metabolism of muscle is low compared with many other tissues, due to its large mass, ∼40% of body weight, its contribution to whole-body resting metabolic rate is appreciable, ∼25%.…”

mentioning

confidence: 99%

“…We have recently identified a new mechanism for thermogenesis in resting muscle, variation in the ATPase activity of the motor protein myosin (5,12,13). Measuring single-cycle ATP turnover rates in skinned resting muscle, we showed that myosin has two states, one with a turnover time of ∼20 s, similar to the rate for purified myosin at 25°C, and one with a turnover time of about 250 s. It had been shown many years earlier by a comparison between the in vivo rate of resting muscle and the activity of purified myosin that the myosin ATPase activity in resting skeletal fibers was highly inhibited (14).…”

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Piperine’s mitigation of obesity and diabetes can be explained by its up-regulation of the metabolic rate of resting muscle

Nogara

Naber

Pate

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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We identify a target for treating obesity and type 2 diabetes, the consumption of calories by an increase in the metabolic rate of resting skeletal muscle. The metabolic rate of skeletal muscle can be increased by shifting myosin heads from the super-relaxed state (SRX), with a low ATPase activity, to a disordered relaxed state (DRX), with a higher ATPase activity. The shift of myosin heads was detected by a change in fluorescent intensity of a probe attached to the myosin regulatory light chain in skinned skeletal fibers, allowing us to perform a highthroughput screen of 2,128 compounds. The screen identified one compound, which destabilized the super-relaxed state, piperine (the main alkaloid component of black pepper). Destabilization of the SRX by piperine was confirmed by single-nucleotide turnover measurements. The effect was only observed in fast twitch skeletal fibers and not in slow twitch fibers or cardiac tissues. Piperine increased ATPase activity of skinned relaxed fibers by 66 ± 15%. The K d was ∼2 μM. Piperine had little effect on the mechanics of either fully active or resting muscle fibers. Previous work has shown that piperine can mitigate both obesity and type 2 diabetes in rodent models of these conditions. We propose that the increase in resting muscle metabolism contributes to these positive effects. The results described here show that up-regulation of resting muscle metabolism could treat obesity and type 2 diabetes and that piperine would provide a useful lead compound for the development of these therapies.myosin | fluorescence | skeletal muscle | super-relaxed state | obesity A n epidemic of obesity and type 2 diabetes is currently affecting a large fraction of the world population (1, 2). This is primarily due to an overconsumption of food coupled with a reduction in physical activity. A natural antidote to both obesity and type 2 diabetes is to choose a healthy lifestyle, including a low-calorie diet and increased physical activity. However, many do not choose this option, and for some advanced patients, increased physical activity is not possible. The response to overfeeding in humans is diverse: some store the excess calories almost entirely, whereas others metabolize most of them (3). The variation is strongly dependent on both lifestyle and genetics. As strenuous activity was limited in some of these protocols, the diversity of weight gain was attributed to light activities, such as fidgeting (3, 4). Alternatively, the diversity may be due to variation in the metabolic rate of resting muscle and to how this responds to activity (5).A pharmacological approach to combating obesity has been of limited value, of the order of 5-10% weight loss when combined with lifestyle changes (for review, see refs. 6 and 7). Therapies for type 2 diabetes produce little effect, with the exception of metformin (for review, see ref. 8). Lifestyle changes, including better diets and increased activity levels, have a larger effect than pharmaceuticals. Here we suggest a target for combating obesity and...

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“…Myosin ATPase capacity and crossbridge formation are regulated at many cellular levels, including isoform expression profiles, conformational states and ion concentrations (Cooke, 2011;Schiaffino and Reggiani, 2011). TH transcriptionally regulates all myosin heavy chain isoforms in mammals (Izumo et al, 1986), but whether this role is conserved in fish is not known.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone regulates muscle function during cold acclimation in zebrafish (Danio rerio)

Little

Seebacher

2013

Journal of Experimental Biology

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SUMMARYThyroid hormone (TH) is a universal regulator of growth, development and metabolism during cold exposure in mammals. In zebrafish (Danio rerio), TH regulates locomotor performance and metabolism during cold acclimation. The influence of TH on locomotor performance may be via its effect on metabolism or, as has been shown in mammals, by modulating muscle phenotypes. Our aim was to determine whether TH influences muscle phenotypes in zebrafish, and whether this could explain changes in swimming capacity in response to thermal acclimation. We used propylthiouracil and iopanoic acid to induce hypothyroidism in zebrafish over a 3-week acclimation period to either 18 or 28°C. To verify that physiological changes following hypothyroid treatment were in fact due to the action of TH, we supplemented hypothyroid fish with 3,5-diiodothryronine (T 2 ) or 3,5,3′-triiodothyronine (T 3 ). Cold-acclimated fish had significantly greater sustained swimming performance (U crit ) but not burst speed. Greater U crit was accompanied by increased tail beat frequency, but there was no change in tail beat amplitude. Hypothyroidism significantly decreased U crit and burst performance, as well as tail beat frequency and SERCA activity in coldacclimated fish. However, myofibrillar ATPase activity increased in cold-acclimated hypothyroid fish. Hypothyroid treatment also decreased mRNA concentrations of myosin heavy chain fast isoforms and SERCA 1 isoform in cold-acclimated fish. SERCA 1 mRNA increased in warm-acclimated hypothyroid fish, and SERCA 3 mRNA decreased in both cold-and warm-acclimated hypothyroid fish. Supplementation with either T 2 or T 3 restored U crit , burst speed, tail beat frequency, SERCA activity and myosin heavy chain and SERCA 1 and 3 mRNA levels of hypothyroid fish back to control levels. We show that in addition to regulating development and metabolism in vertebrates, TH also regulates muscle physiology in ways that affect locomotor performance in fish. We suggest that the role of TH in modulating SERCA1 expression during cold exposure may have predisposed it to regulate endothermic thermogenesis. Supplementary material available online at

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The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle

Cited by 104 publications

References 100 publications

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function

Piperine’s mitigation of obesity and diabetes can be explained by its up-regulation of the metabolic rate of resting muscle

Thyroid hormone regulates muscle function during cold acclimation in zebrafish (Danio rerio)

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