Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
- PMID: 16054090
- DOI: 10.1016/j.cmet.2005.05.002
Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
Abstract
Mammalian cells detect decreases in oxygen concentrations to activate a variety of responses that help cells adapt to low oxygen levels (hypoxia). One such response is stabilization of the protein HIF-1 alpha, a component of the transcription factor HIF-1. Here we show that a small interfering RNA (siRNA) against the Rieske iron-sulfur protein of mitochondrial complex III prevents the hypoxic stabilization of HIF-1 alpha protein. Fibroblasts from a patient with Leigh's syndrome, which display residual levels of electron transport activity and are incompetent in oxidative phosphorylation, stabilize HIF-1 alpha during hypoxia. The expression of glutathione peroxidase or catalase, but not superoxide dismutase 1 or 2, prevents the hypoxic stabilization of HIF-1 alpha. These findings provide genetic evidence that oxygen sensing is dependent on mitochondrial-generated reactive oxygen species (ROS) but independent of oxidative phosphorylation.
Comment in
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ROS: really involved in oxygen sensing.Cell Metab. 2005 Jun;1(6):357-8. doi: 10.1016/j.cmet.2005.05.006. Cell Metab. 2005. PMID: 16054083
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