@article {70007,
	title = {A genetic driver of epileptic encephalopathy impairs gating of synaptic glycolysis},
	journal = {bioRxiv},
	year = {2025},
	month = {2025 Jun 19},
	abstract = {<p>The brain is a disproportionately large consumer of fuel, estimated to expend \~20\% of the whole-body energy budget, and therefore it is critical to adequately control brain fuel expenditures while satisfying its on-demand needs for continued function. The brain is also metabolically vulnerable as the inability to adequately fuel cellular processes that support information transfer between cells leads to rapid neurological impairment. We show here that a genetic driver of early onset epileptic encephalopathy (EOEE), SLC13A5, a Na+/citrate cotransporter (NaCT), is critical for gating the activation of local presynaptic glycolysis. We show that SLC13A5 is in part localized to a presynaptic pool of membrane-bound organelles and acts to transiently clear axonal citrate during electrical activity, in turn activating phosphofructokinase 1. We show that loss of SLC13A5 or mistargeting to the plasma membrane results in suppressed glycolytic gating, activity dependent presynaptic bioenergetic deficits and synapse dysfunction.</p>
},
	doi = {10.1101/2025.06.17.660213},
	url = {https://www.biorxiv.org/content/early/2025/06/19/2025.06.17.660213},
	author = {Koshenov, Zhanat and Kokotos, Alexandros C. and Benedetti, Lorena and Schwartz, Jennifer Lippincott and Ryan, Timothy A.}
}
