A novel type of dietary and metabolic glutamate transporter (dmGLUT) plays a crucial role in megamitochondrial formation in Drosophila

Abstract

Previously, we found that intracellular glutamine accumulation leads to the formation of megamitochondria (MMT) in a Drosophila cell and that two proteins, glutamine synthestase 1 and l(2)01810, play a critical role in the process. However, the function of l(2)01810 has not been elucidated. In this study, we studied the function of l(2)01810 during MMT formation. The overexpression of l(2)01810 and the inhibition of glutamine synthesis showed that l(2)01810 is involved in the accumulation of glutamate. l(2)01810 was predicted to contain transmembrane domains and was found to be localized to the plasma membrane. By using 14C‐labeled glutamate, l(2)01810 was found to uptake glutamate into Drosophila cells in a Na+‐independent manner with high affinity (Km = 69.4 μM). l(2)01810 has a conserved functional domain found usually in vesicular type glutamate transporters and Arg146 in the domain was found to play a key role in glutamate transport and MMT formation. In addition, the analysis of expression patterns of l(2)01810 in adult organs reveals that digestive system, such as the gut, Malpighian tubule and salivary gland, is primarily site where it uptakes glutamate, unlike any other known glutamate transporters which is mainly expressed in the central nervous system (CNS). These results indicate that l(2)01810 is a novel type of glutamate transporter and that glutamate uptake is a rate limiting step for MMT formation.