Basic Biology of Hypoxic Responses Mediated by the Transcription Factor HIFs and Its Implication for Medicine

Oxygen (O(2)) is essential for human life. Molecular oxygen is vital for the production of adenosine triphosphate (ATP) in human cells. O(2) deficiency leads to a reduction in the energy levels that are required to maintain biological functions. O(2) acts as the final acceptor of electrons during oxidative phosphorylation, a series of ATP synthesis reactions that occur in conjunction with the electron transport system in mitochondria. Persistent O(2) deficiency may cause death due to malfunctioning biological processes. The above account summarizes the classic view of oxygen. However, this classic view has been reviewed over the last two decades. Although O(2) is essential for life, higher organisms such as mammals are unable to biosynthesize molecular O(2) in the body. Because the multiple organs of higher organisms are constantly exposed to the risk of “O(2) deficiency,” living organisms have evolved elaborate strategies to respond to hypoxia. In this review, I will describe the system that governs oxygen homeostasis in the living body from the point-of-view of the transcription factor hypoxia-inducible factor (HIF).