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Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells

Author(s)
Fendt, Sarah-Maria; Bell, Eric L.; Mayers, Jared R.; Vokes, Natalie I.; Stephanopoulos, Gregory; Keibler, Mark Andrew; Wasylenko, Thomas Michael; Guarente, Leonard Pershing; Vander Heiden, Matthew G.; Olenchock, Benjamin; ... Show more Show less
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Abstract
Reductively metabolized glutamine is a major cellular carbon source for fatty acid synthesis during hypoxia or when mitochondrial respiration is impaired. Yet, a mechanistic understanding of what determines reductive metabolism is missing. Here we identify several cellular conditions where the α-ketoglutarate/citrate ratio is changed due to an altered acetyl-CoA to citrate conversion, and demonstrate that reductive glutamine metabolism is initiated in response to perturbations that result in an increase in the α-ketoglutarate/citrate ratio. Thus, targeting reductive glutamine conversion for a therapeutic benefit might require distinct modulations of metabolite concentrations rather than targeting the upstream signalling, which only indirectly affects the process.
Date issued
2013-07
URI
http://hdl.handle.net/1721.1/91505
Department
Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Fendt, Sarah-Maria, Eric L. Bell, Mark A. Keibler, Benjamin A. Olenchock, Jared R. Mayers, Thomas M. Wasylenko, Natalie I. Vokes, Leonard Guarente, Matthew G. Vander Heiden, and Gregory Stephanopoulos. “Reductive Glutamine Metabolism Is a Function of the α-Ketoglutarate to Citrate Ratio in Cells.” Nature Communications 4 (July 31, 2013).
Version: Author's final manuscript
ISSN
2041-1723

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