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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Brunelle JK,Bell EL,Quesada NM,Vercauteren K,Tiranti V,Zeviani M,Scarpulla RC,Chandel NSdoi
10.1016/j.cmet.2005.05.002keywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
409-14issue
6eissn
1550-4131issn
1932-7420pii
S1550-4131(05)00140-3journal_volume
1pub_type
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