Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia

Christian M. Metallo, Paulo A. Gameiro, Eric L. Bell, Katherine R. Mattaini, Juanjuan Yang, Karsten Hiller, Christopher M. Jewell, Zachary R. Johnson, Darrell J. Irvine, Leonard Guarente, Joanne K. Kelleher, Matthew G. Vander Heiden, Othon Iliopoulos () and Gregory Stephanopoulos ()
Additional contact information
Christian M. Metallo: Massachusetts Institute of Technology
Paulo A. Gameiro: Massachusetts Institute of Technology
Eric L. Bell: Massachusetts Institute of Technology
Katherine R. Mattaini: Massachusetts Institute of Technology
Juanjuan Yang: Massachusetts General Hospital Cancer Center
Karsten Hiller: Massachusetts Institute of Technology
Christopher M. Jewell: Koch Institute for Cancer Research, Massachusetts Institute of Technology
Zachary R. Johnson: Koch Institute for Cancer Research, Massachusetts Institute of Technology
Darrell J. Irvine: Koch Institute for Cancer Research, Massachusetts Institute of Technology
Leonard Guarente: Massachusetts Institute of Technology
Joanne K. Kelleher: Massachusetts Institute of Technology
Matthew G. Vander Heiden: Massachusetts Institute of Technology
Othon Iliopoulos: Massachusetts General Hospital Cancer Center
Gregory Stephanopoulos: Massachusetts Institute of Technology

Nature, 2012, vol. 481, issue 7381, 380-384

Abstract: Alternative route to fatty acids Oxidative metabolism of glucose has long been considered to be the major provider of carbon for lipid synthesis in animal cells. Two papers in this issue of Nature demonstrate that reductive carboxylation of glutamine is an alternative. Metallo et al. show that various normal and cancerous human cell lines proliferating in hypoxic conditions produce the acetyl-coenzyme A required as a precursor for fatty acid synthesis by the reductive metabolism of glutamine-derived α-ketoglutarate through a pathway requiring isocitrate dehydrogenase 1. Mullen et al. show that tumour cells with defective mitochondria use glutamine-dependent reductive carboxylation as the major pathway of citrate formation. As well as adding a new dimension to our understanding of cell carbohydrate metabolism, this work suggests that there may be potential therapeutic targets along the reductive carboxylation and glutamine catabolic pathways that could prevent hypoxic tumour growth.

Date: 2012
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature10602 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:481:y:2012:i:7381:d:10.1038_nature10602

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature10602

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().