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Reduced ATP turnover during hibernation in relaxed skeletal muscle

Cosimo Napoli, Luisa Schmidt, Mauro Montesel, Laura Cussonneau, Samuele Sanniti, Lorenzo Marcucci, Elena Germinario, Jonas Kindberg, Alina Lynn Evans, Guillemette Gauquelin-Koch, Marco Narici, Fabrice Bertile, Etienne Lefai, Marcus Krüger (), Leonardo Nogara () and Bert Blaauw ()
Additional contact information
Cosimo Napoli: Venetian Institute of Molecular Medicine (VIMM)
Luisa Schmidt: University of Cologne
Mauro Montesel: Venetian Institute of Molecular Medicine (VIMM)
Laura Cussonneau: Venetian Institute of Molecular Medicine (VIMM)
Samuele Sanniti: Venetian Institute of Molecular Medicine (VIMM)
Lorenzo Marcucci: University of Padova
Elena Germinario: University of Padova
Jonas Kindberg: Norwegian Institute for Nature Research
Alina Lynn Evans: Inland Norway University of Applied Sciences
Guillemette Gauquelin-Koch: Centre National d’Etudes Spatiales (CNES)
Marco Narici: University of Padova
Fabrice Bertile: IPHC UMR 7178
Etienne Lefai: CRNH Auvergne
Marcus Krüger: University of Cologne
Leonardo Nogara: Venetian Institute of Molecular Medicine (VIMM)
Bert Blaauw: Venetian Institute of Molecular Medicine (VIMM)

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Hibernating brown bears, due to a drastic reduction in metabolic rate, show only moderate muscle wasting. Here, we evaluate if ATPase activity of resting skeletal muscle myosin can contribute to this energy sparing. By analyzing single muscle fibers taken from the same bears, either during hibernation or in summer, we find that fibers from hibernating bears have a mild decline in force production and a significant reduction in ATPase activity. Single fiber proteomics, western blotting, and immunohistochemical analyses reveal major remodeling of the mitochondrial proteome during hibernation. Furthermore, using bioinformatical approaches and western blotting we find that phosphorylated myosin light chain, a known stimulator of basal myosin ATPase activity, is decreased in hibernating and disused muscles. These results suggest that skeletal muscle limits energy loss by reducing myosin ATPase activity, indicating a possible role for myosin ATPase activity modulation in multiple muscle wasting conditions.

Date: 2025
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DOI: 10.1038/s41467-024-55565-4

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