Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
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.
- Publication:
-
Nature Communications
- Pub Date:
- July 2013
- DOI:
- 10.1038/ncomms3236
- Bibcode:
- 2013NatCo...4.2236F