How HIF-1α Handles Stress

Metazoans cope with hypoxia—oxygen deficiency in the tissues—by eliciting elaborate cellular responses to balance oxygen supply and demand. At the molecular level, adaptation relies primarily on the hypoxia-inducible factor 1α (HIF-1α), a transcription factor, and its binding partner ARNT (also called HIF-1β). This complex activates numerous target genes to limit oxygen consumption and push the cell into survival mode ( 1 ). The scope of HIF-1α action is expanding, though, as it seems to have nontranscriptional activities that reduce DNA replication and slow down cell proliferation when oxygen becomes scarce (see the figure).