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Maintenance of oxygen homeostasis is an indispensable criterion for the existence of multicellular life-forms. Disruption of this homeostasis due to inadequate oxygenation of the respiring tissues leads to pathological hypoxia, which acts as a significant stressor in several pathophysiological conditions including cancer, cardiovascular defects, bacterial infections, and neurological disorders. Consequently, the hypoxic tissues develop necessary adaptations both at the tissue and cellular level. The cellular adaptations involve a dramat