Stabilization of hypoxia-inducible factor-1alpha protein in hypoxia occurs independently of mitochondrial reactive oxygen species production.

ABSTRACT: The transcription factor hypoxia-inducible factor-1α (HIF-1α) is a master regulator of the cellular response to low oxygen. HIF-1α protein accumulates in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic conditions use molecular oxygen to hydroxylate HIF-1α on two conserved proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S proteasome-dependent degradation. A functional mitochondrial electron transport chain is known to be necessary for HIF-1α stabilization in hypoxia. It has been reported that reactive oxygen species (ROS), produced under hypoxia by complex III of the mitochondrial electron transport chain, play a critical role in the stabilization of the HIF-1α protein, possibly by directly inhibiting prolyl hydroxylase enzymes. In c

SUBMITTER: Chua YL 

PROVIDER: S-EPMC2951202 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature