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 language | English (US) |
|---|---|
| Title of host publication | Methods in Enzymology |
| Publisher | Academic Press Inc. |
| Pages | 425-455 |
| Number of pages | 31 |
| Volume | 542 |
| ISBN (Print) | 9780124166189 |
| DOIs | |
| State | Published - 2014 |
Publication series
| Name | Methods in Enzymology |
|---|---|
| Volume | 542 |
| ISSN (Print) | 00766879 |
| ISSN (Electronic) | 15577988 |
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Keywords
- Glycolytic rate
- Intracellular pH
- Mitochondrial autophagy
- Oxygen consumption
- Stable isotope labeling
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
Cite this
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 proceeding › Chapter
}
TY - CHAP
T1 - Analysis of hypoxia-induced metabolic reprogramming
AU - Yang, Chendong
AU - Jiang, Lei
AU - Zhang, Huafeng
AU - Shimoda, Larissa A.
AU - Deberardinis, Ralph J.
AU - Semenza, Gregg L.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Glycolytic rate
KW - Intracellular pH
KW - Mitochondrial autophagy
KW - Oxygen consumption
KW - Stable isotope labeling
UR - http://www.scopus.com/inward/record.url?scp=84901452684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901452684&partnerID=8YFLogxK
U2 - 10.1016/B978-0-12-416618-9.00022-4
DO - 10.1016/B978-0-12-416618-9.00022-4
M3 - Chapter
C2 - 24862279
AN - SCOPUS:84901452684
SN - 9780124166189
VL - 542
T3 - Methods in Enzymology
SP - 425
EP - 455
BT - Methods in Enzymology
PB - Academic Press Inc.
ER -