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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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering
Nature Publishing Group
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).
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