Metabolic Adaptations of Skeletal Muscle Myosin in Hibernating Mammals

Concetti Chiave

Hibernating mammals exhibit species-specific adaptations in skeletal muscle myosin metabolic states to optimize energy utilization during hibernation.

Sintesi

The study investigated the remodeling of skeletal muscle myosin metabolic states in hibernating mammals, including small hibernators (Ictidomys tridecemlineatus and Eliomys quercinus) and large hibernators (Ursus arctos and Ursus americanus).
Key findings:

In large hibernators (U. arctos and U. americanus), the resting myosin conformation and ATP turnover rates were preserved during hibernation.
In small hibernators (I. tridecemlineatus and E. quercinus), the ATP turnover time of relaxed myosin molecules was faster during torpor, especially in type II muscle fibers, leading to increased ATP consumption at ambient temperatures.
At colder temperatures (8°C) mimicking torpor, I. tridecemlineatus showed protection against cold-induced increases in myosin ATP turnover and consumption, suggesting a mechanism to prevent excess heat production.
I. tridecemlineatus exhibited hyper-phosphorylation of the Myh2 protein during torpor, which was predicted to stabilize the myosin filament backbone.
Proteomic analysis revealed hibernation-related changes in sarcomeric and metabolic proteins in I. tridecemlineatus, but not in U. arctos.
These findings demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes in skeletal muscle ATP consumption. Small hibernators appear to have evolved mechanisms to stabilize myosin during torpor to prevent cold-induced increases in energy expenditure and thermogenesis.

Statistiche

Ursus arctos and Ursus americanus did not exhibit changes in the percentage of myosin heads in the disordered-relaxed (DRX) or super-relaxed (SRX) states during hibernation.
In Ictidomys tridecemlineatus and Eliomys quercinus, the ATP turnover time of myosin in the DRX and SRX states was lower during torpor compared to summer active, leading to increased myosin-based ATP consumption.
In Ictidomys tridecemlineatus, lowering the temperature from 20°C to 8°C decreased the DRX and SRX ATP turnover times during active periods, but not during torpor.

Citazioni

"Hibernation is an adaptive strategy employed by many animals aiming to decrease their metabolic rate and improve survival, particularly during harsh, winter conditions where food supply is limited, and thermogenic demands are high."
"Skeletal muscle constitutes approximately 45-55% of body mass and serves as a major determinant of basal metabolic rate and heat production."
"Myosin heads in passive muscle (pCa > 8), can be in different resting metabolic states that maintain a basal level of ATP consumption. In the 'disordered-relaxed' (DRX) state, myosin heads are generally not bound to actin and structurally exist in a conformation (so-called ON state) where they primarily exist freely within the interfilamentous space in the sarcomere. In the 'super-relaxed' (SRX) state, myosin heads adopt a structural conformation against the thick filament backbone (so-called OFF state) [23]. This conformation sterically inhibits the ATPase site on the myosin head, significantly reducing both ATP turnover in these molecules and, therefore heat production."

Approfondimenti chiave tratti da

Remodelling of skeletal muscle myosin metabolic states in hibernating mammals

by Lewis,C. T. ... alle www.biorxiv.org 11-16-2023

https://www.biorxiv.org/content/10.1101/2023.11.14.566992v2

Domande più approfondite

How do the observed myosin metabolic adaptations in hibernating mammals compare to other physiological conditions involving metabolic depression, such as starvation or hypoxia?

The observed myosin metabolic adaptations in hibernating mammals, particularly the small hibernators like I. tridecemlineatus and E. quercinus, showcase a unique response to metabolic depression compared to other physiological conditions like starvation or hypoxia. In hibernating mammals, there is a specific modulation of myosin dynamics, with alterations in the proportions of myosin DRX and SRX conformations to reduce ATP/metabolic demand during torpor. This is in contrast to conditions like starvation or hypoxia, where the focus is more on energy conservation and survival rather than the fine-tuning of metabolic processes. Additionally, the myosin stabilization mechanisms observed in hibernating small mammals are tailored to the specific requirements of hibernation, such as the need to reduce heat production during torpor while maintaining muscle function. This contrasts with the adaptations seen in conditions like starvation, where the emphasis may be more on preserving muscle mass and function despite limited nutrient availability.

What are the potential implications of the myosin stabilization mechanisms observed in small hibernators for the treatment of muscle wasting disorders or age-related sarcopenia?

The myosin stabilization mechanisms observed in small hibernators, particularly the hyper-phosphorylation of Myh2 leading to increased protein stability during torpor, hold significant implications for the treatment of muscle wasting disorders and age-related sarcopenia. By understanding how these mechanisms contribute to the regulation of myosin dynamics and energy expenditure in skeletal muscle, researchers and clinicians can potentially develop targeted interventions to prevent or mitigate muscle wasting in various conditions. For instance, strategies that mimic the hyper-phosphorylation of Myh2 to stabilize the myosin filament backbone could be explored as a therapeutic approach to prevent muscle atrophy and improve muscle function in individuals with muscle wasting disorders or age-related sarcopenia. Additionally, insights into the role of myosin in non-shivering thermogenesis could lead to the development of novel therapies that target muscle metabolism to enhance heat production and energy expenditure in a controlled manner, which may have implications for managing conditions associated with abnormal thermoregulation.

Could the insights into myosin's role in non-shivering thermogenesis in hibernating mammals inform the development of novel therapeutic approaches for disorders involving abnormal thermoregulation?

The insights into myosin's role in non-shivering thermogenesis in hibernating mammals, particularly the small hibernators like I. tridecemlineatus, have the potential to inform the development of novel therapeutic approaches for disorders involving abnormal thermoregulation. Understanding how myosin dynamics and ATP turnover contribute to heat production and energy expenditure in skeletal muscle during hibernation can provide valuable insights into the mechanisms of non-shivering thermogenesis. By targeting specific pathways or molecules involved in regulating myosin conformation and ATP consumption, researchers may be able to develop targeted therapies for disorders characterized by abnormal thermoregulation, such as hypothermia or hyperthermia. For example, modulating myosin ATP turnover rates or stabilizing myosin in specific conformations could be explored as strategies to regulate heat production and energy expenditure in conditions where thermoregulation is compromised. These novel therapeutic approaches could offer new avenues for managing disorders involving abnormal thermoregulation and optimizing metabolic responses in various physiological states.