MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Seagroves, T. N.
Right arrow Articles by Johnson, R. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seagroves, T. N.
Right arrow Articles by Johnson, R. S.

Molecular and Cellular Biology, May 2001, p. 3436-3444, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3436-3444.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells

Tiffany N. Seagroves,1 Heather E. Ryan,1 Han Lu,1 Bradly G. Wouters,2 Merrill Knapp,3 Pierre Thibault,4 Keith Laderoute,3 and Randall S. Johnson1,*

Molecular Biology Section, Division of Biology, University of California San Diego, La Jolla, California 920931; University of Ottawa and the Ottawa Regional Cancer Centre, Ottawa, Ontario K1H 8L6,2 and Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario K1A 0R6,4 Canada; and SRI International, Menlo Park, California 940253

Received 15 November 2000/Returned for modification 20 December 2000/Accepted 13 February 2001

The ability to respond to differential levels of oxygen is important to all respiring cells. The response to oxygen deficiency, or hypoxia, takes many forms and ranges from systemic adaptations to those that are cell autonomous. Perhaps the most ancient of the cell-autonomous adaptations to hypoxia is a metabolic one: the Pasteur effect, which includes decreased oxidative phosphorylation and an increase in anaerobic fermentation. Because anaerobic fermentation produces far less ATP than oxidative phosphorylation per molecule of glucose, increased activity of the glycolytic pathway is necessary to maintain free ATP levels in the hypoxic cell. Here, we present genetic and biochemical evidence that, in mammalian cells, this metabolic switch is regulated by the transcription factor HIF-1. As a result, cells lacking HIF-1alpha exhibit decreased growth rates during hypoxia, as well as decreased levels of lactic acid production and decreased acidosis. We show that this decrease in glycolytic capacity results in dramatically lowered free ATP levels in HIF-1alpha -deficient hypoxic cells. Thus, HIF-1 activation is an essential control element of the metabolic state during hypoxia; this requirement has important implications for the regulation of cell growth during development, angiogenesis, and vascular injury.

* Corresponding author. Mailing address: Division of Biology, University of California, San Diego, 1212 Pacific Hall, Mail code 0366, 9500 Gilman Dr., La Jolla, CA 92093. Phone: (858) 822-0509. Fax: (858) 534-5831. E-mail: rjohnson{at}biomail.ucsd.edu.

Molecular and Cellular Biology, May 2001, p. 3436-3444, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3436-3444.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.