caa a22 4500 606176217 CHVBK 20210128100746.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00018-015-2025-9 doi (NATIONALLICENCE)springer-10.1007/s00018-015-2025-9 HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology [Elektronische Daten] [F. Favier, F. Britto, D. Freyssenet, X. Bigard, H. Benoit] Skeletal muscle is a metabolically active tissue and the major body protein reservoir. Drop in ambient oxygen pressure likely results in a decrease in muscle cells oxygenation, reactive oxygen species (ROS) overproduction and stabilization of the oxygen-sensitive hypoxia-inducible factor (HIF)-1α. However, skeletal muscle seems to be quite resistant to hypoxia compared to other organs, probably because it is accustomed to hypoxic episodes during physical exercise. Few studies have observed HIF-1α accumulation in skeletal muscle during ambient hypoxia probably because of its transient stabilization. Nevertheless, skeletal muscle presents adaptations to hypoxia that fit with HIF-1 activation, although the exact contribution of HIF-2, I kappa B kinase and activating transcription factors, all potentially activated by hypoxia, needs to be determined. Metabolic alterations result in the inhibition of fatty acid oxidation, while activation of anaerobic glycolysis is less evident. Hypoxia causes mitochondrial remodeling and enhanced mitophagy that ultimately lead to a decrease in ROS production, and this acclimatization in turn contributes to HIF-1α destabilization. Likewise, hypoxia has structural consequences with muscle fiber atrophy due to mTOR-dependent inhibition of protein synthesis and transient activation of proteolysis. The decrease in muscle fiber area improves oxygen diffusion into muscle cells, while inhibition of protein synthesis, an ATP-consuming process, and reduction in muscle mass decreases energy demand. Amino acids released from muscle cells may also have protective and metabolic effects. Collectively, these results demonstrate that skeletal muscle copes with the energetic challenge imposed by O2 rarefaction via metabolic optimization. Springer Basel, 2015 Altitude nationallicence Atrophy nationallicence Hypoxia inducible factor nationallicence Metabolism nationallicence Mitochondria nationallicence Oxidative stress nationallicence Favier F. INRA, UMR 866 Dynamique Musculaire et Métabolisme, 34060, Montpellier, France aut Britto F. INRA, UMR 866 Dynamique Musculaire et Métabolisme, 34060, Montpellier, France aut Freyssenet D. Laboratoire de Physiologie de l'Exercice EA 4338, Université de Lyon, Université Jean Monnet, 42000, Saint Etienne, France aut Bigard X. Agence Française de Lutte contre le Dopage, 75007, Paris, France aut Benoit H. INSERM, U1042 Hypoxie Physio-Pathologie, 38000, Grenoble, France aut Cellular and Molecular Life Sciences Springer International Publishing 72/24(2015-12-01), 4681-4696 1420-682X 72:24<4681 2015 72 18 https://doi.org/10.1007/s00018-015-2025-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-2025-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Favier F. INRA, UMR 866 Dynamique Musculaire et Métabolisme, 34060, Montpellier, France aut NATIONALLICENCE 700 1- Britto F. INRA, UMR 866 Dynamique Musculaire et Métabolisme, 34060, Montpellier, France aut NATIONALLICENCE 700 1- Freyssenet D. Laboratoire de Physiologie de l'Exercice EA 4338, Université de Lyon, Université Jean Monnet, 42000, Saint Etienne, France aut NATIONALLICENCE 700 1- Bigard X. Agence Française de Lutte contre le Dopage, 75007, Paris, France aut NATIONALLICENCE 700 1- Benoit H. INSERM, U1042 Hypoxie Physio-Pathologie, 38000, Grenoble, France aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer International Publishing 72/24(2015-12-01), 4681-4696 1420-682X 72:24<4681 2015 72 18