Inter-connection between mitochondria and HIFs.

The transcription factors hypoxia inducible factors 1 and 2 (HIF-1 and HIF-2) regulate multiple responses to physiological hypoxia such as transcription of the hormone erythropoietin to enhance red blood cell proliferation, vascular endothelial growth factor to promote angiogenesis and glycolytic enzymes to increase glycolysis. Recent studies indicate that HIFs also regulate mitochondrial respiration and mitochondrial oxidative stress. Interestingly, mitochondrial metabolism, respiration and oxidative stress also regulate activation of HIFs. In this review, we examine the evidence that mitochondria and HIFs are intimately connected to regulate each other resulting in appropriate responses to hypoxia.