Displacing hexokinase from mitochondrial voltage-dependent anion channel impairs GLT-1-mediated glutamate uptake but does not disrupt interactions between GLT-1 and mitochondrial proteins.

摘要: The glutamate transporter GLT-1 is the major route for clearance of extracellular in forebrain, and most protein found astrocytes. This coupled to Na+-electrochemical gradient, supporting active intracellular accumulation glutamate. We recently used a proteomic approach identify proteins that may interact with rat cortex, including Na+/K+-ATPase, glycolytic enzymes, several mitochondrial proteins. also showed puncta (~70%) are overlapped by mitochondria astroglial processes organotypic slices. Based on this analysis, we proposed enzyme hexokinase 1 (HK1) might physically form scaffold link because HK1 known outer membrane protein, voltage-dependent anion channel (VDAC). In present study, first validated interactions between HK-1, VDAC using forward reverse immunoprecipitations. provided evidence subfraction co-localizes vivo. peptide, disrupt interaction HK VDAC, did not parallel experiments, displacement from reduced GLT-1-mediated uptake. These results suggest although forms co-immunoprecipitatable complexes both GLT-1, it does However, supports transport activity.