Tissue specificity of mitochondrial adaptations in rats after 4 weeks of normobaric hypoxia

Document Type

Journal Article




School of Medical and Health Sciences


Originally published as: Ferri, A., Panariti, A., Miserocchi, G., Rocchetti, M., Comani, G. B., Rivolta, I., & Bishop, D. J. (2018). Tissue specificity of mitochondrial adaptations in rats after 4 weeks of normobaric hypoxia. European journal of applied physiology, 118(8) pp 1641-1652. Original article available here


Purpose Exposure to hypoxia has been suggested to activate multiple adaptive pathways so that muscles are better able to maintain cellular energy homeostasis. However, there is limited research regarding the tissue specificity of this response. The aim of this study was to investigate the influence of tissue specificity on mitochondrial adaptations of rat skeletal and heart muscles after 4 weeks of normobaric hypoxia (FiO2: 0.10).

Methods Twenty male Wistar rats were randomly assigned to either normobaric hypoxia or normoxia. Mitochondrial respiration was determined in permeabilised muscle fibres from left and right ventricles, soleus and extensorum digitorum longus (EDL). Citrate synthase activity and the relative abundance of proteins associated with mitochondrial biogenesis were also analysed.

Results After hypoxia exposure, only the soleus and left ventricle (both predominantly oxidative) presented a greater maximal mass-specific respiration (+48 and +25%, p < 0.05) and mitochondrial-specific respiration (+75 and +28%, p < 0.05). Citrate synthase activity was higher in the EDL (0.63 ± 0.08 vs 0.41 ± 0.10 μmol min− 1 μg− 1) and lower in the soleus (0.65 ± 0.17 vs 0.87 ± 0.20 μmol min− 1 μg− 1) in hypoxia with respect to normoxia. There was a lower relative protein abundance of PGC-1α (−25%, p < 0.05) in the right ventricle and a higher relative protein abundance of PGC-1β (+43%, p < 0.05) in the left ventricle of rats exposed to hypoxia, with few differences for protein abundance in the other muscles.

Conclusion Our results show a muscle-specific response to 4 weeks of normobaric hypoxia. Depending on fibre type, and the presence of ventricular hypertrophy, muscles respond differently to the same degree of environmental hypoxia.