At extreme altitude, prolonged and severe hypoxia menaces human function and survival, and also associated with profound loss of muscle mass which results into a debilitating critical illness of skeletal muscle atrophy . Hypobaric hypoxia altered redox homeostasis and impaired calcium ion handling in skeletal muscles . Dysregulated Ca homeostasis and activated calpain is the prime stressor in high altitude hypoxia while the reason for subsequent abnormal release of pathological Ca into cytoplasm is largely unexplored . The present study identified the redox remodeling in the Ca release channel, Ryanodine Receptor (RyR1) owing to its hypernitrosylation state in skeletal muscles in chronic hypobaric hypoxia exposed rats . RyR1-hypernitrosylation decreases the binding of FKBP12/calstabin-1 and other complexes from the channel, causing``leakiness"in RyR1 ion-channel . A strong RyR1 stabilizer, S107 enhanced binding affinity of FKBP12 with hypernitrosylated RyR1, reduced Sarco (endo) plasmic reticulum (SR) Ca leak and improved muscle strength and function under chronic hypoxia . Administration of S107 inhibited the skeletal muscle damage, maintained ultrastructure of sarcomere and sarcolemmal integrity . Histological analysis proved the increase in cross-sectional area of myofibers . Further, the number of apoptotic cells was also reduced by S107 treatment . Conclusively, we proposed that the redox remodeling of RyR1 (hypernitrosylated-RyR1) might be responsible for dysregulated Ca homeostasis which consequently impaired muscle strength and function in response to chronic hypoxic stress . Reduced SR Ca leak and enhanced binding affinity of FKBP12 may provide a novel therapeutic avenue in ameliorating skeletal muscle atrophy at high altitude.