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Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation.

Authors
  • Brunelle, Joslyn K
  • Bell, Eric L
  • Quesada, Nancy M
  • Vercauteren, Kristel
  • Tiranti, Valeria
  • Zeviani, Massimo
  • Scarpulla, Richard C
  • Chandel, Navdeep S
Type
Published Article
Journal
Cell Metabolism
Publisher
Elsevier
Publication Date
Jun 01, 2005
Volume
1
Issue
6
Pages
409–414
Identifiers
PMID: 16054090
Source
Medline
License
Unknown

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.

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