Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
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-ket...
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/91505 https://orcid.org/0000-0002-8956-5117 https://orcid.org/0000-0002-8607-1787 https://orcid.org/0000-0002-6702-4192 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0003-4064-2510 https://orcid.org/0000-0001-6909-4568 |
| Summary: | 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. |
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