Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells

Tiffany Seagroves, H. E. Ryan, H. Lu, B. G. Wouters, M. Knapp, P. Thibault, K. Laderoute, R. S. Johnson

Research output: Contribution to journalArticle

404 Citations (Scopus)

Abstract

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-1α 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-1α-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.

Original languageEnglish (US)
Pages (from-to)3436-3444
Number of pages9
JournalMolecular and cellular biology
Volume21
Issue number10
DOIs
StatePublished - May 9 2001

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Transcription Factors
Adenosine Triphosphate
Oxidative Phosphorylation
Fermentation
Vascular System Injuries
Acidosis
Growth and Development
Molecular Biology
Lactic Acid
Hypoxia
Oxygen
Glucose
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. / Seagroves, Tiffany; Ryan, H. E.; Lu, H.; Wouters, B. G.; Knapp, M.; Thibault, P.; Laderoute, K.; Johnson, R. S.

In: Molecular and cellular biology, Vol. 21, No. 10, 09.05.2001, p. 3436-3444.

Research output: Contribution to journalArticle

Seagroves, T, Ryan, HE, Lu, H, Wouters, BG, Knapp, M, Thibault, P, Laderoute, K & Johnson, RS 2001, 'Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells', Molecular and cellular biology, vol. 21, no. 10, pp. 3436-3444. https://doi.org/10.1128/MCB.21.10.3436-3444.2001
Seagroves, Tiffany ; Ryan, H. E. ; Lu, H. ; Wouters, B. G. ; Knapp, M. ; Thibault, P. ; Laderoute, K. ; Johnson, R. S. / Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. In: Molecular and cellular biology. 2001 ; Vol. 21, No. 10. pp. 3436-3444.
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