Janus, or the inevitable battle between too much and too little oxygen

: Oxygen levels are key regulators of virtually every living mammalian cell, both under physiological and pathological conditions. Starting from embryonic and fetal development, through growth, onset and progression of diseases, oxygen is a subtle, although pivotal, mediator of key processes such as differentiation, proliferation, autophagy, necrosis and apoptosis. Hypoxia-driven modifications of cellular physiology are deeply investigated for the clinical and translational relevance, especially in the ischemic scenario. The mild or severe lack of oxygen is undoubtedly related to cell death although abundant evidence points at oscillating oxygen levels, instead of permanent low pO2, as the most detrimental factor. Different cell types can consume oxygen at different rates and, most interestingly, some cells can shift from low to high consumption according to the metabolic demand. Hence, we can assume that, in the intracellular compartment, oxygen tension varies from low to high levels depending on both supply and consumption. The positive balance between supply and consumption leads to a pro-oxidative environment, with some cell types facing hypoxia/hyperoxia cycles, while some others are under fairly constant oxygen tension. Within this frame, the alterations of oxygen levels (dysoxia) are critical in two paradigmatic organs, heart the brain, under physiological and pathological conditions and the interactions of oxygen with other physiologically relevant gases, such as nitric oxide, can alternatively contribute to the worsening or protection of ischemic organs. Furthermore, the effects of dysoxia is of pivotal importance for iron metabolism.