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PMID: 17551816 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

HIF-1 mediates the Warburg effect in clear cell renal carcinoma.

Journal of bioenergetics and biomembranes ·Vol. 39 ·No. 3 ·2007-06-00 ·Pages 231-4

Semenza GL

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis in all metazoan species. O(2)-dependent hydroxylation of two proline residues in the HIF-1alpha subunit is necessary for the binding of the von Hippel-Lindau (VHL) protein, which is a component of a ubiquitin protein ligase that ubiquitinates HIF-1alpha, leading to its degradation by the proteasome. In the majority of cases of the clear cell type of renal carcinoma, both VHL genes are inactivated by mutation or epigenetic silencing, leading to dysregulated HIF-1 transcriptional activity. VHL loss-of-function leads, under aerobic conditions, to a HIF-1-dependent reprogramming of glucose and energy metabolism that includes increased glucose uptake, glycolysis, and lactate production accompanied by a reciprocal decrease in respiration. These findings delineate for the first time the molecular mechanisms underlying the Warburg effect in a human cancer.

MeSH Terms
Animals Carcinoma, Renal Cell/metabolism Glucose/metabolism Glycolysis Humans Hypoxia-Inducible Factor 1/physiology Hypoxia-Inducible Factor 1, alpha Subunit/physiology Kidney Neoplasms/metabolism Lactic Acid/metabolism Mitochondria/physiology Oxidative Phosphorylation Oxygen/physiology Proteasome Endopeptidase Complex/physiology Protein Binding Pyruvic Acid/metabolism Von Hippel-Lindau Tumor Suppressor Protein/metabolism
Chemicals
Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Lactic Acid Pyruvic Acid Von Hippel-Lindau Tumor Suppressor Protein Proteasome Endopeptidase Complex Glucose Oxygen
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Semenza Gregg L
Institute for Cell Engineering, Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology, and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. [email protected]
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Article Info
Journal
Journal of bioenergetics and biomembranes
Abbr.
J Bioenerg Biomembr
ISSN
0145-479X
DOI
10.1007/s10863-007-9081-2
Email
[email protected]
Published
2007-06-00
Pages
231-4
Language
English
Region
United States
NLM ID
7701859
Subset
IM
External Links
PubMed source DOI: 10.1007/s10863-007-9081-2 View journal details
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