AGC1/2, the mitochondrial aspartate-glutamate carriers
AGC1/2, the mitochondrial aspartate-glutamate carriers
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DOI：
10.1016/j.bbamcr.2016.04.011
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发表时间：
2016-10-01
影响因子：
5.1
通讯作者：
Rossignol, R.
中科院分区：
文献类型：
--
作者：
Amoedo, N. D.;Punzi, G.;Rossignol, R.
本文综述了天冬氨酸/谷氨酸转运体（AGC1-arthrin和AGC2-citrin）的结构和功能。这些蛋白质将线粒体基质内合成的天冬氨酸提供给细胞质，以交换谷氨酸和质子。AGC载波的结构还不可用，但是提出了比较3D模型。此外，通过使用重组AGC1和AGC2，重组到脂质体囊泡中进行的运输试验，允许探索这些载体的动力学，并揭示其特定的运输特性。AGCs参与广泛的细胞功能，如控制线粒体呼吸、钙信号和抗氧化防御。AGC1也可能发挥特殊的组织特异性功能，因为它被发现参与视网膜中的细胞间代谢共生。另一方面，AGC1参与谷氨酸介导的神经元兴奋性毒性，并且在罕见的人类疾病中发现AGC基因或蛋白质改变。因此，AGC1基因敲除的小鼠模型表现为生长延迟和全身性震颤，并伴有髓鞘形成缺陷。最近，AGC被认为在肿瘤代谢中起着至关重要的作用，如从代谢组学研究中观察到的，该研究表明，由AGC1从细胞内输出的谷胱甘肽被用于细胞溶质谷胱甘肽的再生。因此，鉴于AGCs在细胞代谢和人类病理学中的中心作用，目前正在开发药物筛选以鉴定这些载体的药理学调节剂。这篇文章是由Pierre Sonveaux，Pierre Maechler和Jean-Claude Martinou编辑的线粒体通道特刊的一部分。(C)2016爱思唯尔B.V.保留所有权利。
In this review we discuss the structure and functions of the aspartate/glutamate carriers (AGC1-aralar and AGC2-citrin). Those proteins supply the aspartate synthesized within mitochondrial matrix to the cytosol in exchange for glutamate and a proton. A structure of an AGC carrier is not available yet but comparative 3D models were proposed. Moreover, transport assays performed by using the recombinant AGC1 and AGC2, reconstituted into liposome vesicles, allowed to explore the kinetics of those carriers and to reveal their specific transport properties. AGCs participate to a wide range of cellular functions, as the control of mitochondrial respiration, calcium signaling and antioxydant defenses. AGC1 might also play peculiar tissue-specific functions, as it was found to participate to cell-to-cell metabolic symbiosis in the retina. On the other hand, AGC1 is involved in the glutamate-mediated excitotoxicity in neurons and AGC gene or protein alterations were discovered in rare human diseases. Accordingly, a mice model of AGC1 gene knock-out presented with growth delay and generalized tremor, with myelinisation defects. More recently, AGC was proposed to play a crucial role in tumor metabolism as observed from metabolomic studies showing that the asparate exported from the mitochondrion by AGC1 is employed in the regeneration of cytosolic glutathione. Therefore, given the central role of AGCs in cell metabolism and human pathology, drug screening are now being developed to identify pharmacological modulators of those carriers. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. (C) 2016 Elsevier B.V. All rights reserved.