De Napoli Cosimo, Schmidt Luisa, Montesel Mauro, Cussonneau Laura, Sanniti Samuele, Marcucci Lorenzo, Germinario Elena, Kindberg Jonas, Evans Alina Lynn, Gauquelin-Koch Guillemette, Narici Marco, Bertile Fabrice, Lefai Etienne, Krüger Marcus, Nogara Leonardo, Blaauw Bert
Venetian Institute of Molecular Medicine (VIMM), Padova, Italy.
Department of Biomedical Sciences, 35131, University of Padova, Padova, Italy.
Nat Commun. 2025 Jan 2;16(1):80. doi: 10.1038/s41467-024-55565-4.
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.
冬眠的棕熊由于代谢率急剧下降，仅表现出中度的肌肉萎缩。在此，我们评估静息骨骼肌肌球蛋白的ATP酶活性是否有助于这种能量节约。通过分析取自同一熊在冬眠期间或夏季的单根肌纤维，我们发现来自冬眠熊的肌纤维在力量产生方面有轻微下降，ATP酶活性显著降低。单纤维蛋白质组学、蛋白质免疫印迹和免疫组织化学分析揭示了冬眠期间线粒体蛋白质组的主要重塑。此外，使用生物信息学方法和蛋白质免疫印迹，我们发现磷酸化肌球蛋白轻链（一种已知的基础肌球蛋白ATP酶活性刺激物）在冬眠和废用的肌肉中减少。这些结果表明，骨骼肌通过降低肌球蛋白ATP酶活性来限制能量损失，这表明肌球蛋白ATP酶活性调节在多种肌肉萎缩状况中可能发挥作用。
