Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation.

TitleOxygen sensing requires mitochondrial ROS but not oxidative phosphorylation.
Publication TypeJournal Article
Year of Publication2005
AuthorsBrunelle, JK, Bell, EL, Quesada, NM, Vercauteren, K, Tiranti, V, Zeviani, M, Scarpulla, RC, Chandel, NS
JournalCell Metab
Volume1
Issue6
Pagination409-14
Date Published2005 Jun
ISSN1550-4131
KeywordsElectron Transport Complex III, Hydrogen Peroxide, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Mitochondria, Oxidative Phosphorylation, Oxygen, Reactive Oxygen Species, Signal Transduction, Transcription Factors
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.

DOI10.1016/j.cmet.2005.05.002
Alternate JournalCell Metab.
Citation Key10.1016/j.cmet.2005.05.002
PubMed ID16054090
Grant ListGM60472-06 / GM / NIGMS NIH HHS / United States
P01HL071643-01A4 / HL / NHLBI NIH HHS / United States