Article, 2024
Remodeling of skeletal muscle myosin metabolic states in hibernating mammals
eLife,
ISSN
2050-084X,
Volume 13,
Page rp94616,
10.7554/elife.94616
Contributors
Lewis, Christopher T A
0000-0003-4477-422X
(Corresponding author)
[1]
Melhedegaard, Elise G
0000-0002-8605-7707
[1]
Ognjanovic, Marija M
[1]
Olsen, Mathilde S
0009-0003-1320-5152
[1]
Laitila, Jenni M
[1]
Seaborne, Robert A E
0000-0003-2491-3747
[1]
[2]
Gronset, Magnus
0000-0002-2582-5063
[1]
Zhang, Changxin
[3]
Iwamoto, Hiroyuki
[4]
Hessel, Anthony L
0000-0003-4278-4221
[5]
[6]
Kuehn, Michel N
[5]
[6]
Merino, Carla
0000-0002-8793-5516
[7]
Amigó, Núria
0000-0002-0116-9145
[7]
Fröbert, Ole
0000-0002-5846-345X
[8]
[9]
Giroud, Sylvain
0000-0001-6621-7462
[10]
[11]
Staples, James F
[12]
Goropashnaya, Anna V
[13]
Fedorov, Vadim B
[13]
Barnes, Brian M
[13]
Tøien, Øivind
0000-0001-5967-2483
[13]
Drew, Kelly L
0000-0002-2436-5720
[13]
Sprenger, Ryan J
0000-0002-0891-0848
[14]
Ochala, Julien
0000-0002-6358-2920
(Corresponding author)
[1]
Affiliations
- [1]
University of Copenhagen
[NORA names:
KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
- [2]
King's College London
[NORA names:
United Kingdom; Europe, Non-EU; OECD];
- [3]
University of Michigan–Ann Arbor
[NORA names:
United States; America, North; OECD];
- [4]
SPring-8
[NORA names:
Japan; Asia, East; OECD];
- [5]
Accelerated Muscle Biotechnologies Consultants, Boston, United States
[NORA names:
United States; America, North; OECD];
(... more)
- [6]
University of Münster
[NORA names:
Germany; Europe, EU; OECD];
- [7]
Biosfer Teslab, Reus, Spain
[NORA names:
Spain; Europe, EU; OECD];
- [8]
Aarhus University
[NORA names:
AU Aarhus University;
University; Denmark; Europe, EU; Nordic; OECD];
- [9]
Örebro University
[NORA names:
Sweden; Europe, EU; Nordic; OECD];
- [10]
Northern Michigan University
[NORA names:
United States; America, North; OECD];
- [11]
University of Veterinary Medicine Vienna
[NORA names:
Austria; Europe, EU; OECD];
- [12]
Western University
[NORA names:
Canada; America, North; OECD];
- [13]
University of Alaska Fairbanks
[NORA names:
United States; America, North; OECD];
- [14]
University of British Columbia
[NORA names:
Canada; America, North; OECD]
(less)
Abstract
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.
Keywords
ATP,
ATP consumption,
ATP demand,
MANT-ATP,
MYH2,
X-ray,
X-ray diffraction,
active period,
alterations,
ambient lab temperature,
analysis,
changes,
chase experiments,
cold exposure,
consumption,
demand,
diffraction,
dynamics,
efficiency,
energy,
energy expenditure,
energy utilization,
expenditure,
experiments,
exposure,
fast-twitch muscle fibers,
fibers,
hibernating mammals,
hibernation,
hyper-phosphorylation,
increase,
isolated muscle fibers,
lab temperature,
levels,
mammal species,
mammals,
mechanism,
metabolic efficiency,
metabolic state,
metabolic suppression,
molecular mechanisms,
molecules,
muscle,
muscle energy expenditure,
muscle fibers,
muscle myosin,
muscle non-shivering thermogenesis,
myosin,
myosin dynamics,
myosin molecules,
myosin structure,
non-shivering thermogenesis,
period,
periods of torpor,
preservation,
proteomic analysis,
proteomics,
remodeling,
response,
response to cold exposure,
results,
skeletal muscle,
skeletal muscle myosin,
species,
state,
structure,
study,
suppression,
temperature,
thermogenesis,
torpor,
type,
type II,
type II muscle fibers,
utilization,
winter,
winter period
Funders
Data Provider: Digital Science