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

24 Citations (Scopus)

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 publicationMethods in Enzymology
PublisherAcademic Press Inc.
Pages425-455
Number of pages31
Volume542
ISBN (Print)9780124166189
DOIs
StatePublished - 2014

Publication series

NameMethods in Enzymology
Volume542
ISSN (Print)00766879
ISSN (Electronic)15577988

Fingerprint

Glucose
Hypoxia-Inducible Factor 1
Acetyl Coenzyme A
Metabolism
Fatty Acids
Cells
Switches
Physiological Adaptation
Sodium-Hydrogen Antiporter
Gene encoding
Citric Acid Cycle
Facilitative Glucose Transport Proteins
Autophagy
Glutamine
Adenoviridae
Tumors
Lactic Acid
Neoplasms
Up-Regulation
Fluxes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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 Methods in Enzymology (Vol. 542, pp. 425-455). (Methods in Enzymology; Vol. 542). Academic Press Inc.. https://doi.org/10.1016/B978-0-12-416618-9.00022-4

Analysis of hypoxia-induced metabolic reprogramming. / Yang, Chendong; Jiang, Lei; Zhang, Huafeng; Shimoda, Larissa A.; Deberardinis, Ralph J.; Semenza, Gregg L.

Methods in Enzymology. Vol. 542 Academic Press Inc., 2014. p. 425-455 (Methods in Enzymology; Vol. 542).

Research output: Chapter in Book/Report/Conference proceedingChapter

Yang, C, Jiang, L, Zhang, H, Shimoda, LA, Deberardinis, RJ & Semenza, GL 2014, Analysis of hypoxia-induced metabolic reprogramming. in Methods in Enzymology. vol. 542, Methods in Enzymology, vol. 542, Academic Press Inc., pp. 425-455. https://doi.org/10.1016/B978-0-12-416618-9.00022-4
Yang C, Jiang L, Zhang H, Shimoda LA, Deberardinis RJ, Semenza GL. Analysis of hypoxia-induced metabolic reprogramming. In Methods in Enzymology. Vol. 542. Academic Press Inc. 2014. p. 425-455. (Methods in Enzymology). https://doi.org/10.1016/B978-0-12-416618-9.00022-4
Yang, Chendong ; Jiang, Lei ; Zhang, Huafeng ; Shimoda, Larissa A. ; Deberardinis, Ralph J. ; Semenza, Gregg L. / Analysis of hypoxia-induced metabolic reprogramming. Methods in Enzymology. Vol. 542 Academic Press Inc., 2014. pp. 425-455 (Methods in Enzymology).
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