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Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation

2005; Cell Press; Volume: 1; Issue: 6 Linguagem: Inglês

10.1016/j.cmet.2005.05.002

1932-7420

Joslyn K. Brunelle, Eric L. Bell, Nancy Quesada, Kristel Vercauteren, Valeria Tiranti, Massimo Zeviani, Richard C. Scarpulla, Navdeep S. Chandel,

Nitric Oxide and Endothelin Effects

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-1α, 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-1α 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-1α during hypoxia. The expression of glutathione peroxidase or catalase, but not superoxide dismutase 1 or 2, prevents the hypoxic stabilization of HIF-1α. These findings provide genetic evidence that oxygen sensing is dependent on mitochondrial-generated reactive oxygen species (ROS) but independent of oxidative phosphorylation.