Does interplay between nitric oxide and mitochondria affect hypoxia-inducible transcription factor-1 activity?

TitleDoes interplay between nitric oxide and mitochondria affect hypoxia-inducible transcription factor-1 activity?
Publication TypeJournal Article
Year of Publication2003
AuthorsMurphy, MP
JournalBiochem J
Volume376
IssuePt 2
Paginatione5-6
Date Published2003 Dec 01
ISSN1470-8728
KeywordsCell Hypoxia, Cell Respiration, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Mitochondria, Nitric Oxide, Transcription Factors
Abstract

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-1alpha stability. HIF-1alpha, 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-1alpha stability. Close to hypoxia, low NO concentrations destabilized HIF-1alpha by inhibiting mitochondrial respiration, thereby increasing the local oxygen concentration. In contrast, high NO concentrations stabilized HIF-1alpha at both high and low oxygen concentrations by a non-mitochondrial pathway. These data resolve reported discrepancies on the effect of NO on HIF-1alpha stability at low oxygen concentrations and suggest that inhibition of mitochondrial respiration by NO may affect oxygen sensing by HIF-1 in vivo.

DOI10.1042/BJ20031605
Alternate JournalBiochem. J.
Citation Key10.1042/BJ20031605
PubMed ID14627433
PubMed Central IDPMC1223796