The Role of Hypoxia and Hypoxia Signaling in Skeletal Muscle Physiology

Hypoxia and hypoxia signaling play an integral role in regulating skeletal muscle physiology. Environmental hypoxia and tissue hypoxia in muscles cue for their appropriate physiological response and adaptation, and cause an array of cellular and metabolic changes. In addition, muscle stem cells (satellite cells), exist in a hypoxic state, and this intrinsic hypoxic state correlates with their quiescence and stemness. The mechanisms of hypoxia-mediated regulation of satellite cells and myogenesis are yet to be characterized, and their seemingly contradicting effects reported leave their exact roles somewhat perplexing. This review summarizes the recent findings on the effect of hypoxia and hypoxia signaling on the key aspects of muscle physiology, namely, stem cell maintenance and myogenesis with a particular attention given to distinguish the intrinsic versus local hypoxia in an attempt to better understand their respective regulatory roles and how their relationship affects the overall response. This review further describes their mechanistic links and their possible implications on the relevant pathologies and therapeutics.