Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

538 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
JournalCell Metabolism
Volume1
Issue number6
DOIs
StatePublished - Jun 2005

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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