Abstract PR07: Functional identification of a mitochondrial glutamine carrier using isotope tracers

Abstract

Abstract Mitochondria are the central metabolic hub of cells, and cells have the ability to metabolize numerous substrates in biochemical pathways within these organelles. Glutamine is a vital nutrient that serves as both nitrogen carrier and anaperotic substrate for mammalian cells. Various cancer cells exhibit dependence on glutaminolysis to fuel bioenergetic and biosynthetic metabolic pathways. This pathway is catalyzed, in part, via mitochondrial glutaminase; however, the mechanism through which glutamine is transported into the matrix is not well known. In fact, the function of nearly half the known mitochondrial solute carriers (SLC25 family) is yet to be described. Using a combination of cell engineering strategies, metabolic tracing using 15N and 13C labeled substrates, and respirometry applied to both intact and permeabilized cultures we have identified a putative mitochondrial glutamine carrier (MQC). Knockdown of this carrier decreases cell growth and drives cells to use alternate pathways for oxidation of glutamine in the TCA cycle. Cancer cells treated with inhibitors of glutaminase exhibit a similar metabolic phenotype as demonstrated via 13C tracing. These results functionally identify a critical node in mitochondrial metabolism and further highlight the utility of metabolic tracing and mass spectrometry for elucidating metabolic function. Citation Format: Christian Metallo. Functional identification of a mitochondrial glutamine carrier using isotope tracers. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr PR07.