Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Elise G Melhedegaard
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Marija M Ognjanovic
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Mathilde S Olsen
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Jenni Laitila
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Robert AE Seaborne
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Centre for Human and Applied Physiological Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, United Kingdom
Magnus Gronset
Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
Changxin Zhang
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States
Hiroyuki Iwamoto
Spring-8, Japan Synchrotron Radiation Research Institute, Hyogo, Japan
Anthony L Hessel
Institute of Physiology II, University of Muenster, Muenster, Germany; Accelerated Muscle Biotechnologies Consultants, Boston, United States
Michel N Kuehn
Institute of Physiology II, University of Muenster, Muenster, Germany; Accelerated Muscle Biotechnologies Consultants, Boston, United States
Carla Merino
Biosfer Teslab, Reus, Spain
Nuria Amigo
Biosfer Teslab, Reus, Spain
Ole Frobert
Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; Faculty of Health, Department of Cardiology, Örebro University, Örebro, Sweden
Energetics Lab, Department of Biology, Northern Michigan University, Marquette, United States; Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine Vienna, Vienna, Austria
James F Staples
Department of Biology, University of Western Ontario, London, Canada
Anna V Goropashnaya
Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, United States
Vadim B Fedorov
Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, United States
Brian Barnes
Center for Transformative Research in Metabolism, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, United States
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.
