The Preservation of Muscle Mitochondrial Machinery During Hypometabolic Hibernation in Scandinavian Brown Bears (Ursus arctos)

Aim: Unlike humans, brown bears (Ursus arctos) uniquely preserve skeletal muscle mass and function during months of hibernation despite prolonged fasting and inactivity. We investigated how mitochondrial energetics respond in skeletal muscle to support this remarkable resilience. Methods: Muscle biopsies from eight wild brown bears were collected during hibernation and again in the active summer season. We assessed mitochondrial respiration using high-resolution respirometry and evaluated changes in protein expression, enzyme activity, and mitochondrial content through proteomics, Western blotting, enzymatic assays, and DNA quantification. Results: Hibernation was associated with lower mitochondrial respiratory capacity, largely due to a reduction in mitochondrial density rather than damage or dysfunction. Despite reduced SDH subunit expression in the whole skeletal muscle, SDH activity remained stable. This likely reflects post-translational regulation and increased, or at least maintained, functional efficiency of the remaining Complex II, allowing mitochondrial respiration to shift toward Complex II-mediated electron entry during hibernation. Proteomic analyses revealed targeted adjustments that maintained energy efficiency, supported both fat and carbohydrate oxidation at low temperatures, and minimized energy loss. Additionally, selective downregulation of mitochondrial dynamic proteins may help protect against muscle degradation. Conclusion: These findings highlight a temperature-sensitive, multifaceted strategy that preserves mitochondrial energetics during prolonged inactivity, despite reduced mitochondrial density. The selective maintenance of electron flow and fuel flexibility offers novel insights for mitigating muscle wasting in sedentary or immobilized humans.