Hypoxia-inducible factor

Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia.

Overview

Hypoxia-inducible factors are a family of heterodimeric transcription factors that are most commonly activated in response to low oxygen conditions, or hypoxia. They play an essential role in the body's response to hypoxia by activating the transcription of many genes including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia.

Structure

HIFs are heterodimers consisting of an alpha subunit and a beta subunit. The alpha subunit is unstable under normoxic conditions and is constantly synthesized and degraded. However, under hypoxic conditions, the alpha subunit is stabilized, dimerizes with the beta subunit and is translocated to the nucleus where it binds to hypoxia response elements (HREs) in the promoter region of target genes.

Function

The primary function of HIFs is to regulate oxygen homeostasis in both unicellular and multicellular organisms. They are involved in the regulation of a variety of genes that play crucial roles in adaptation to low oxygen conditions. These include genes involved in angiogenesis, erythropoiesis, cell cycle, apoptosis, and glucose metabolism.

Clinical significance

HIFs have been implicated in the pathophysiology of various diseases including cancer, ischemic diseases, and chronic lung diseases. They are also involved in the pathogenesis of chronic kidney disease and have been implicated in the progression of renal fibrosis.

See also

• Oxygen
• Transcription factor
• Angiogenesis
• Apoptosis
• Glucose metabolism