Analysis of hypoxia-induced metabolic reprogramming

Chendong Yang, Lei Jiang, Huafeng Zhang, Larissa A. Shimoda, Ralph J. Deberardinis, Gregg L. Semenza

Research output: Chapter in Book/Report/Conference proceedingChapter

35 Scopus citations

Abstract

Hypoxia is a common finding in advanced human tumors and is often associated with metastatic dissemination and poor prognosis. Cancer cells adapt to hypoxia by utilizing physiological adaptation pathways that promote a switch from oxidative to glycolytic metabolism. This promotes the conversion of glucose into lactate while limiting its transformation into acetyl coenzyme A (acetyl-CoA). The uptake of glucose and the glycolytic flux are increased under hypoxic conditions, mostly owing to the upregulation of genes encoding glucose transporters and glycolytic enzymes, a process that depends on hypoxia-inducible factor 1 (HIF-1). The reduced delivery of acetyl-CoA to the tricarboxylic acid cycle leads to a switch from glucose to glutamine as the major substrate for fatty acid synthesis in hypoxic cells. In addition, hypoxia induces (1) the HIF-1-dependent expression of BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) and BNIP3-like (BNIP3L), which trigger mitochondrial autophagy, thereby decreasing the oxidative metabolism of both fatty acids and glucose, and (2) the expression of the sodium-hydrogen exchanger NHE1, which maintains an alkaline intracellular pH. Here, we present a compendium of methods to study hypoxia-induced metabolic alterations.

Original languageEnglish (US)
Title of host publicationConceptual Background and Bioenergetic/Mitochondrial Aspects of Oncometabolism
PublisherAcademic Press Inc.
Pages425-455
Number of pages31
ISBN (Print)9780124166189
DOIs
StatePublished - 2014

Publication series

NameMethods in Enzymology
Volume542
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • Glycolytic rate
  • Intracellular pH
  • Mitochondrial autophagy
  • Oxygen consumption
  • Stable isotope labeling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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  • Cite this

    Yang, C., Jiang, L., Zhang, H., Shimoda, L. A., Deberardinis, R. J., & Semenza, G. L. (2014). Analysis of hypoxia-induced metabolic reprogramming. In Conceptual Background and Bioenergetic/Mitochondrial Aspects of Oncometabolism (pp. 425-455). (Methods in Enzymology; Vol. 542). Academic Press Inc.. https://doi.org/10.1016/B978-0-12-416618-9.00022-4