In addition to being an amino acid that is incorporated into proteins, glutamate is the most abundant neurotransmitter in the mammalian CNS, the precursor for the inhibitory neurotransmitter γ-aminobutyric acid, and one metabolic step from the tricarboxylic acid cycle intermediate α-ketoglutarate. Extracellular glutamate is cleared by a family of Na+-dependent transporters. These transporters are variably expressed by all cell types in the nervous system, but the bulk of clearance is into astrocytes. GLT-1 and GLAST (also called EAAT2 and EAAT1) mediate this activity and are extremely abundant proteins with their expression enriched in fine astrocyte processes. In this review, we will focus on three topics related to these astrocytic glutamate transporters. First, these transporters co-transport three Na+ ions and a H+ with each molecule of glutamate and counter-transport one K+; they are also coupled to a Cl- conductance. The movement of Na+ is sufficient to cause profound astrocytic depolarization, and the movement of H+ is linked to astrocytic acidification. In addition, the movement of Na+ can trigger the activation of Na+ co-transporters (e.g. Na+-Ca2+ exchangers). We will describe the ways in which these ionic movements have been linked as signals to brain function and/or metabolism. Second, these transporters co-compartmentalize with mitochondria, potentially providing a mechanism to supply glutamate to mitochondria as a source of fuel for the brain. We will provide an overview of the proteins involved, discuss the evidence that glutamate is oxidized, and then highlight some of the un-resolved issues related to glutamate oxidation. Finally, we will review evidence that ischemic insults (stroke or oxygen/glucose deprivation) cause changes in these astrocytic mitochondria and discuss the ways in which these changes have been linked to glutamate transport, glutamate transport-dependent signaling, and altered glutamate metabolism. We conclude with a broader summary of some of the unresolved issues.

中文翻译：

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谷氨酸转运蛋白和线粒体：信号传导，共室化，功能性耦合和未来方向。

谷氨酸不仅是蛋白质中的氨基酸，而且是哺乳动物中枢神经系统中含量最丰富的神经递质，是抑制性神经递质γ-氨基丁酸的前体，是三羧酸循环中间体α-酮戊二酸的一个代谢步骤。细胞外谷氨酸被Na +依赖性转运蛋白家族清除。这些转运蛋白在神经系统中的所有细胞类型中均有差异表达，但大部分清除进入星形胶质细胞。GLT-1和GLAST（也称为EAAT2和EAAT1）介导此活性，并且是极为丰富的蛋白质，其表达富含精细的星形胶质细胞过程。在这篇综述中，我们将重点介绍与这些星形细胞谷氨酸转运蛋白有关的三个主题。第一，这些转运蛋白与谷氨酸的每个分子共同转运三个Na +离子和一个H +，并反向转运一个K +。它们还与Cl电导耦合。Na +的移动足以引起深层的星形细胞去极化，而H +的移动与星形细胞的酸化有关。另外，Na +的移动可以触发Na +共转运子（例如Na +-Ca 2+交换子）的活化。我们将描述这些离子运动作为大脑功能和/或新陈代谢的信号所关联的方式。第二，这些转运蛋白与线粒体共同分隔，潜在地提供了向线粒体供应谷氨酸作为大脑燃料来源的机制。我们将提供有关蛋白质的概述，讨论谷氨酸被氧化的证据，然后重点介绍一些与谷氨酸氧化有关的未解决的问题。最后，我们将综述缺血性损伤（中风或氧/葡萄糖剥夺）导致这些星形细胞线粒体发生变化的证据，并讨论将这些变化与谷氨酸转运，谷氨酸转运依赖性信号传导和谷氨酸代谢改变相关的方式。最后，我们对一些未解决的问题进行了更广泛的总结。