Bert Blaauw
Department of Biomedical Sciences
University of Padova
Padova, Italy

Hibernation as countermeasure for spaceflight muscle atrophy?

Bert Blaauw^1,2,*, Cosimo De Napoli^1,2§, Luisa Schmidt^3§, Mauro Montesel^1,2, Laura Cussonneau_^1,2, Samuele Sanniti¹, Lorenzo Marcucci², Elena Germinario², Jonas Kindberg^4,5, Alina Lynn Evans⁶, Guillemette Gauquelin-Koch⁷, Marco Narici², Fabrice Bertile^8,9, Etienne Lefai¹⁰, Marcus Krüger^{3, *}, Leonardo Nogara^1,2,11,*

¹Venetian Institute of Molecular Medicine (VIMM), Via Orus 2, 35129, Padova, Italy
²Department of Biomedical Sciences, 35137, University of Padova, Padova, Italy
³Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany
⁴Norwegian Institute for Nature Research, Trondheim, Norway.
⁵Department of Wildlife, Fish and Environmental Studies, Umeå, Sweden
⁶Department of Forestry and Wildlife Management, Koppang, Norway
⁷French Space Agency, Centre National d'Etudes Spatiales (CNES), Paris, France
⁸Université de Strasbourg, CNRS, IPHC UMR 7178, 23 rue du Loess, 67037, Strasbourg Cedex 2, France
⁹National Proteomics Infrastructure, ProFi, FR2048 Strasbourg, France
¹⁰Université Clermont Auvergne, INRAE, UNH UMR 1019, 63000 Clermont-Ferrand, France
¹¹Department of Pharmaceutical Sciences, 35137, University of Padova, Padova, Italy


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.

Fundings
This work was supported by grants from Association Française contre les Myopathies (AFMTéléthon to B.B., no. 24357), Associazione Italiana per la Ricerca sul Cancro (AIRC)-27007 to B.B. This work is supported by the European Union – NextGenerationEU, by the 2021 STARS Grants@Unipd programme and Association Française contre les Myopathies (AFMTéléthon, no. 24328) granted to L. N., This work was supported by the European Union EU-NMJ-Chip (JPND2019-466-146), EU-NMJ-Chip (FKZ:01ED2006), and the Deutsche Forschungsgemeinschaft DFG FOR2722/2 (DFG 384170921) to MK. French Space Agency (CNES, #7906 and #8072) to F.B., and Agence Nationale de la Recherche (ANR-22-CE14-0018) to F.B. and E.L.