Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation.

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 Metab

journal_title

Cell metabolism

authors

Brunelle JK,Bell EL,Quesada NM,Vercauteren K,Tiranti V,Zeviani M,Scarpulla RC,Chandel NS

doi

10.1016/j.cmet.2005.05.002

keywords:

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

409-14

issue

6

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(05)00140-3

journal_volume

1

pub_type

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