Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
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Stephanopoulos_Reductive glutamine.pdf
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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
Date Issued
July 2013
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/ncomms3236
