This Commentary discusses recent results from the laboratory of Salvador Moncada (Mateo et al., in this issue of the Biochemical Journal) that shed light on the interaction of nitric oxide (NO) and the transcription factor hypoxia-inducible factor 1 (HIF-1). Using cells stably transfected with inducible NO synthase (iNOS) under the control of a tetracycline-inducible promoter, they generated a range of NO concentrations and determined how these affected HIF-1α stability. HIF-1α, a component of the heterodimer HIF-1, is rapidly degraded at high oxygen concentrations, and thus HIF-1 is only active as a transcription factor under hypoxic conditions. The authors found a biphasic effect of NO concentration on HIF-1α stability. Close to hypoxia, low NO concentrations destabilized HIF-1α by inhibiting mitochondrial respiration, thereby increasing the local oxygen concentration. In contrast, high NO concentrations stabilized HIF-1α at both high and low oxygen concentrations by a non-mitochondrial pathway. These data resolve reported discrepancies on the effect of NO on HIF-1α stability at low oxygen concentrations and suggest that inhibition of mitochondrial respiration by NO may affect oxygen sensing by HIF-1 in vivo.
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November 2003
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Commentary|
November 15 2003
Does interplay between nitric oxide and mitochondria affect hypoxia-inducible transcription factor-1 activity?
Michael P. MURPHY
Michael P. MURPHY
1
MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K.
1e-mail mpm@mrc-dunn.cam.ac.uk
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Publisher: Portland Press Ltd
Received:
October 21 2003
Accepted:
October 21 2003
Accepted Manuscript online:
November 24 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 376 (1): e5–e6.
Article history
Received:
October 21 2003
Accepted:
October 21 2003
Accepted Manuscript online:
November 24 2003
Citation
Michael P. MURPHY; Does interplay between nitric oxide and mitochondria affect hypoxia-inducible transcription factor-1 activity?. Biochem J 15 November 2003; 376 (1): e5–e6. doi: https://doi.org/10.1042/bj20031605
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