TY - JOUR T1 - The <em>Drosophila</em> mitochondrial citrate carrier regulates L-2-hydroxyglutarate accumulation by coupling the tricarboxylic acid cycle with glycolysis JF - bioRxiv DO - 10.1101/297705 SP - 297705 AU - Hongde Li AU - Alexander J. Hurlburt AU - Jason M. Tennessen Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/04/09/297705.abstract N2 - The oncometabolites D- and L-2-hydroxyglutarate (2HG) broadly interfere with cellular metabolism, physiology, and gene expression. A key regulator of 2HG metabolism is the mitochondrial citrate carrier (CIC), which, when mutated, promotes excess D-/L-2HG accumulation. The mechanism by which CIC influences 2HG levels, however, remains unknown. Here we studied the Drosophila gene scheggia (sea), which encodes the fly CIC homolog, to explore the mechanisms linking mitochondrial citrate efflux to L-2HG metabolism. Our findings demonstrate that decreased Drosophila CIC activity results in elevated glucose catabolism and increased lactate production, thereby creating a metabolic environment that inhibits L-2HG degradation. ER -