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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Vaux, E. C. Articles by Ratcliffe, P. J. Search for Related Content PubMed PubMed Citation Articles by Vaux, E. C. Articles by Ratcliffe, P. J. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2001, Vol. 98, No. 2, pp. 296-302 HEMATOPOIESIS Regulation of hypoxia-inducible factor is preserved in the absence of a functioning mitochondrial respiratory chain Emma C. Vaux, Eric Metzen, Kay M. Yeates, and Peter J. Ratcliffe From The Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom. Hypoxia-inducible factor (HIF) mediates a large number of transcriptional responses to hypoxia and has an important role in processes that include angiogenesis and erythropoiesis. The HIF DNA binding complex consists of 2 basic-helix-loop-helix PAS proteins designated  and  subunits. Regulation occurs principally through the  subunits, which are stabilized and activated in hypoxia. Although substantial evidence implicates reactive oxygen species (ROS) in the regulatory process, the precise mechanisms remain unclear. Mitochondria are an important source of ROS, and in one model it has been proposed that hypoxia increases the generation of ROS at complex III in the mitochondrion and that this signal acts through a transduction pathway to stabilize HIF-1 and to activate HIF. To test this model the induction of the HIF-1 subunit and the HIF target gene, glucose-transporter-1, was examined in a variety of mutant cells that lacked mitochondrial DNA (0) or had other genetic defects in mitochondrial respiration. HIF induction by hypoxia was essentially normal in all cells tested. Hydrogen peroxide production was measured by the luminol/peroxidase method and found to be reduced in 0 versus wild-type cells and reduced by hypoxia in both 0 and wild-type cells. Furthermore, concentrations of rotenone that maximally inhibited respiration did not affect HIF activation by hypoxia. These data do not support the model outlined above and indicate that a functional respiratory chain is not necessary for the regulation of HIF by oxygen. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. L. Deshmane, R. Mukerjee, S. Fan, L. Del Valle, C. 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