TY - JOUR

T1 - Remodeling of skeletal muscle myosin metabolic states in hibernating mammals

AU - Lewis, Christopher T.A.

AU - Melhedegaard, Elise G.

AU - Ognjanovic, Marija M.

AU - Olsen, Mathilde S.

AU - Laitila, Jenni

AU - Seaborne, Robert A.E.

AU - Gronset, Magnus

AU - Zhang, Changxin

AU - Iwamoto, Hiroyuki

AU - Hessel, Anthony L.

AU - Kuehn, Michel N.

AU - Merino, Carla

AU - Amigo, Nuria

AU - Frobert, Ole

AU - Giroud, Sylvain

AU - Staples, James F.

AU - Goropashnaya, Anna V.

AU - Fedorov, Vadim B.

AU - Barnes, Brian

AU - Toien, Oivind

AU - Drew, Kelly

AU - Sprenger, Ryan J.

AU - Ochala, Julien

N1 - Publisher Copyright: © 2024, Lewis et al.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - biochemistry

KW - cell biology

KW - chemical biology

KW - eliomys quercinus

KW - ictidomys tridecemlineatus

KW - ursus americanus

KW - ursus arctos

UR - http://www.scopus.com/inward/record.url?scp=85193386663&partnerID=8YFLogxK

U2 - 10.7554/eLife.94616

DO - 10.7554/eLife.94616

M3 - Journal article

C2 - 38752835

AN - SCOPUS:85193386663

VL - 13

JO - eLife

JF - eLife

SN - 2050-084X

M1 - RP94616

ER -