Since multicellular organisms depend on ATP produced by oxidative phosphorylation in mitochondria, O 2 is the bare necessity for life. The organism develops multiple protective mechanisms against hypoxia during evolution. Mammals will adapt rapidly to hypoxia via enhancing respiratory and cardiac functions. Furthermore, adrenaline secreted from adrenal chromaffin cells increases the blood glucose concentration via glucogenolysis in the liver and enhances the cardiac function via ␤ receptors;

more »

... s results in a greater supply of glucose as a fuel to the tissues under hypoxic conditions. The third of short-term adaptations is hypoxic pulmonary vasoconstriction (HPV). When some areas of the lung become hypoventilated, the blood circulation to such areas is restricted. As a result, the extent of circulation in the lung areas is matched to that of ventilation. Besides these shortterm adaptations, organisms will adapt to the lifethreatening insult via transcription in the nucleus (long-term response). Renal and liver cells increase the production of erythropoietin, thereby increasing red blood cells with an increase in O 2 transport. Al-though it is not clear whether the mechanisms for O 2sensing are common for these short and long-term responses, an increase in intracellular concentration of Ca 2ϩ ions ([Ca 2ϩ ] i ) because of voltage-dependent Ca 2ϩ influx plays an essential role for the transduction of O 2 signal in short term responses [1-3]. Since a change in reactive oxygen species (ROS) production was suggested to play a major role for hypoxia detection in smooth muscle (SM) cells [4, 5] and the understanding of the mitochondrial production of ROS helps in elucidating O 2 -sensing mechanisms in other cells, we will first discuss where ROS is produced in mitochondria and whether ROS production increases or decreases in response to hypoxia. Then the mechanisms for O 2 -sensing in SM cells in small pulmonary arteries, carotid body type I cells, adrenal medullary cells, and liver cells will be considered. Mitochondrial Production of ROS It is generally believed that 2% of O 2 consumed in mi- Abstract: Since O 2 is the bare necessity for multicellular organisms, they develop multiple protective mechanisms against hypoxia. Mammals will adapt to hypoxia in short and long terms. The short-term responses include enhancement of the respiratory and cardiac functions, adrenaline secretion from adrenal medullary cells, and pulmonary vasoconstriction, whereas the long-term response is the increase in erythropoietin production with the consequent increase in red blood cells. Although much work has been done to elucidate molecular mechanisms for O 2 -sensing for the last ten years, the majority of the mechanisms remain unclear. We will review mechanisms proposed for hypoxia detection in carotid body type I cells, pulmonary artery smooth muscle, adrenal medullary cells, and liver cells, with the special focus on adrenal medullary cells.