@inbook{9f1f5b7de59d4b45a9769f7a27704aa1,
title = "Analysis of hypoxia-induced metabolic reprogramming",
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.",
keywords = "Glycolytic rate, Intracellular pH, Mitochondrial autophagy, Oxygen consumption, Stable isotope labeling",
author = "Chendong Yang and Lei Jiang and Huafeng Zhang and Shimoda, {Larissa A.} and Deberardinis, {Ralph J.} and Semenza, {Gregg L.}",
year = "2014",
doi = "10.1016/B978-0-12-416618-9.00022-4",
language = "English (US)",
isbn = "9780124166189",
series = "Methods in Enzymology",
publisher = "Academic Press Inc.",
pages = "425--455",
booktitle = "Conceptual Background and Bioenergetic/Mitochondrial Aspects of Oncometabolism",
}