HIF-1: hypoxia-inducible factor or dysoxia-inducible factor?

Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes involved in diverse aspects of cellular and integrative physiology, including energy metabolism, cell growth, survival, invasion, migration or angiogenesis. The activity of this transcription factor is known to be increased by hypoxia, but also by a growing number of apparently unrelated factors that can activate it even in nonhypoxic conditions. Here I propose a model in which an alteration in oxygen metabolism is the key cellular event involved in HIF-1 activation under hypoxic and nonhypoxic conditions. This new perspective unifies previously unrelated observations and predicts cellular processes and therapeutic strategies that may modify HIF-1 activity. This may have relevance, for instance, to cancer, as HIF-1 overexpression is observed in many human cancers and has been associated with increased patient mortality.