Researchers have make clear the molecular mechanisms underlying hibernation, publishing their findings in the present day as a Reviewed Preprint in eLife.
Their analysis, in small and huge hibernating mammals, is described by the editors as an vital examine advancing our information of the position of myosin construction and power consumption on the molecular mechanisms of hibernation, backed by strong methodology and proof. The findings additionally recommend myosin — a kind of motor protein concerned in muscle contraction — performs a task in non-shivering thermogenesis throughout hibernation, the place warmth is produced impartial of the muscle exercise of shivering.
Hibernation is a survival technique utilized by many animals, characterised by a state of deep dormancy and profound reductions in metabolic exercise, physique temperature, coronary heart price and respiration. Throughout hibernation, animals depend on saved power reserves, notably fat, to maintain their bodily features. The metabolic slowdown permits hibernators to preserve power and endure lengthy intervals of meals shortage and harsh environmental circumstances throughout winter. Nevertheless, the underlying mobile and molecular mechanisms behind hibernation stay incompletely understood.
Smaller hibernating mammals expertise prolonged bouts of a hypo-metabolic state referred to as torpor, which considerably decreases their physique temperature and is punctuated by spontaneous intervals of interbout euthermic arousals (IBA) — the place they briefly increase their physique temperature to revive some physiological features, similar to eliminating waste and consuming extra meals. This contrasts with bigger mammals, whose physique temperature is far much less decreased throughout hibernation and stays pretty constant. Skeletal muscle, which contains round half of a mammal’s physique mass, performs a key position in figuring out their warmth manufacturing and power use.
“Till lately, power consumption in skeletal muscle groups was regarded as primarily linked to the exercise of myosin, which is concerned in muscle contraction. Nevertheless, there may be rising proof that, even when they’re relaxed, skeletal muscle groups nonetheless use a small quantity of power,” explains lead writer Christopher Lewis, a postdoctoral researcher on the Division of Biomedical Sciences, College of Copenhagen, Denmark. “Myosin heads in passive muscle groups may be in several resting states: the ‘disordered-relaxed’, or DRX state, and the ‘super-relaxed’, or SRX state. Myosin heads within the DRX state deplete ATP — the power forex of the cell — between 5 to 10 occasions sooner than these within the SRX state.”
Lewis and colleagues hypothesised that modifications within the proportion of myosin within the DRX or SRX states might contribute to the decreased power use seen throughout hibernation. To check this, they took skeletal muscle samples from two small hibernators — the 13-lined floor squirrel and the Backyard dormouse — and two massive hibernators — the American black bear and brown bear.
First, they appeared to determine whether or not the myosin states, and their respective ATP consumption charges, had been totally different between energetic intervals and hibernation. They checked out muscle fibres taken from the 2 bear species throughout their energetic summer season section (SA), and their winter hibernation interval. They discovered no variations within the proportion of myosin within the DRX or SRX state between the 2 phases. To measure the speed of ATP consumption by myosin, they used a specialised check referred to as the Mant-ATP chase assay. This revealed that there have been additionally no modifications within the power consumption charges of myosin. This can be to forestall the onset of great muscular wastage in bears throughout hibernation.
The crew additionally carried out the Mant-ATP chase assay on samples taken from the small mammals throughout SA, IBA and torpor. As within the bigger hibernators, they didn’t observe any variations within the proportion of myosin heads within the SRX or DRX formation between the three phases. Nevertheless, they did uncover that the ATP turnover time of myosin molecules in each formations was decrease in IBA and torpor in comparison with the SA section, resulting in an surprising general improve in ATP consumption.
As small mammals bear a extra vital drop in physique temperature throughout hibernation than massive mammals, the crew examined whether or not this surprising improve in ATP consumption additionally occurred at a decrease temperature. They re-ran the Mant-ATP chase assay at 8°C, in comparison with the ambient lab temperature of 20°C used beforehand. Reducing the temperature decreased DRX and SRX-linked ATP turnover occasions in SA and IBA, resulting in a rise in ATP consumption. Metabolic organs, similar to skeletal muscle, are well-known to extend core physique temperature in response to vital chilly publicity, both by inducing shivering or by non-shivering thermogenesis. Chilly publicity precipitated a rise in ATP consumption by myosin in samples obtained throughout SA and IBA, suggesting that myosin might contribute to non-shivering thermogenesis in small hibernators.
The crew didn’t observe cold-induced modifications in myosin power consumption in samples obtained throughout torpor. They recommend that that is seemingly a protecting mechanism to keep up the low core physique temperature, and wider metabolic shutdown, seen throughout torpor.
Lastly, the researchers wished to grasp the modifications that happen on the protein stage throughout the totally different hibernating phases. They assessed whether or not hibernation impacts the construction of two myosin proteins from the 13-lined floor squirrel: Myh7 and Myh2. Though they didn’t observe any hibernation-related modifications within the construction of Myh7, they found that Myh2 underwent vital phosphorylation — a course of essential for power storage — throughout torpor, in comparison with SA and IBA. Additionally they analysed the construction of the 2 proteins within the brown bear, discovering no structural variations between SA and hibernation. They due to this fact conclude that Myh2 hyper-phosphorylation is particularly related to torpor, somewhat than hibernation generally, and suggest that this serves to extend myosin stability in small mammals. This will likely act as a possible molecular mechanism to mitigate myosin-associated will increase in skeletal muscle expenditure in response to chilly publicity in periods of torpor.
eLife’s editors word that some areas of the examine warrant additional examine. Specifically, the muscle samples had been taken solely from the legs of the animals studied. Given the core physique and limbs have totally different temperatures, investigating muscle samples from different areas of the physique would additional validate the crew’s findings.
“Altogether, our findings recommend that ATP turnover variations in DRX and SRX myosin states happen in small mammals just like the 13-lined floor squirrel throughout hibernation in chilly environments. In distinction, bigger mammals just like the American black bear present no such modifications, seemingly because of their steady physique temperature throughout hibernation,” concludes senior writer Julien Ochala, Affiliate Professor on the Division of Biomedical Sciences, College of Copenhagen. “Our outcomes additionally recommend that myosin might act as a contributor to skeletal muscle non-shivering thermogenesis throughout hibernation.”
