The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production.

ABSTRACT: Mammalian cells increase transcription of genes for adaptation to hypoxia through the stabilization of hypoxia-inducible factor 1alpha (HIF-1alpha) protein. How cells transduce hypoxic signals to stabilize the HIF-1alpha protein remains unresolved. We demonstrate that cells deficient in the complex III subunit cytochrome b, which are respiratory incompetent, increase ROS levels and stabilize the HIF-1alpha protein during hypoxia. RNA interference of the complex III subunit Rieske iron sulfur protein in the cytochrome b-null cells and treatment of wild-type cells with stigmatellin abolished reactive oxygen species (ROS) generation at the Qo site of complex III. These interventions maintained hydroxylation of HIF-1alpha protein and prevented stabilization of HIF-1alpha protein during hypoxia

SUBMITTER: Bell EL 

PROVIDER: S-EPMC2064363 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature