Glutamine transport in brain mitochondria

Gin is transported into rat brain synaptic and non-synaptic mitochondria by a protein catalyzed process. The uptake is significantly higher in synapti c than in non-synaptic mitochondria. The transport is inhibited by the amin o acids Glu, Asn and Asp, and by the TCA cycle intermediates succinate, mal ate and 2-OG. The inhibition by 2-OG is counteracted by AOA and is therefor e assumed to be due to transamination of 2-OG, whereby Glu is formed. This presumes that Glu also binds to an inhibitory site on the matrix face of th e inner membrane. The transport is complex and cannot be explained by the s imple uniport mechanism which has been proposed for renal (Schoolwerth and LaNoue, 1985), and liver mitochondria (Soboll et al., 1991). Thus, Gin tran sport is stimulated by respiration and by the proton electrochemical gradie nt. Since it is indicated that both the neutral Gin zwitterion and the Gin anion are transported, there are probably different uptake mechanisms, but not necessarily different carriers. Gin may be transported by an electroneu tral mechanism as a proton compensated anion, as well as electrophoreticall y as a zwitterion with a proton, and probably also by diffusion as a zwitte rion. The properties of the brain mitochondrial Gin uptake mechanisms are a lso not identical with those of a purified renal Gin transporter. It is pos sible that the Gin transport is controlled by more than one protein, which may be situated on distinct species in a heterogeneous mitochondrial popula tion. Since Gin is assumed to participate in energy production as well as i n the synthesis of nucleic acid components and proteins in brain mitochondr ia, the control of Gin uptake in these organelles may be important. (C) 200 0 Elsevier Science Ltd. All rights reserved.