RESUMO
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.
Assuntos
Ácido Aspártico/metabolismo , Proteínas de Ligação ao Cálcio/fisiologia , Ácido Glutâmico/metabolismo , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Transportadores de Ânions Orgânicos/fisiologia , Sequência de Aminoácidos , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Proteínas de Ligação ao Cálcio/genética , Bovinos , Sequência Consenso , Humanos , Malatos/metabolismo , Camundongos , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Proteínas de Transporte da Membrana Mitocondrial/deficiência , Proteínas de Transporte da Membrana Mitocondrial/genética , Modelos Moleculares , NAD/metabolismo , Proteínas de Neoplasias/fisiologia , Especificidade de Órgãos , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/genética , Oxirredução , Conformação Proteica , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
A case of primary low grade B cell lymphoma of the salivary gland associated with a low grade B cell lymphoma of the thymus and involvement of the skin is reported. The lesions in the salivary gland and in the thymus showed the typical features of a lymphoma arising from the mucosa associated lymphoid tissue (MALT) and comprised lymphatic follicles, centrocyte-like (CCL) cells and lymphoepithelial lesions. Immunohistochemistry and Southern blot analysis supported the hypothesis that these lesions can originate from the same cellular clone. These findings confirm the occurrence of low grade B cell MALT lymphoma in the thymus and the possibility of spread of MALT lymphoma to other mucosal sites.