Publications

• Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria.

  Palmieri L., Pardo B., Lasorsa F.M., del Arco A., Kobayashi K., Iijima M., Runswick M.J., Walker J.E., Saheki T., Satrustegui J., Palmieri F.

  The mitochondrial aspartate/glutamate carrier catalyzes an important step in both the urea cycle and the aspartate/malate NADH shuttle. Citrin and aralar1 are homologous proteins belonging to the mitochondrial carrier family with EF-hand Ca(2+)-binding motifs in their N-terminal domains. Both prot ... >> More

  The mitochondrial aspartate/glutamate carrier catalyzes an important step in both the urea cycle and the aspartate/malate NADH shuttle. Citrin and aralar1 are homologous proteins belonging to the mitochondrial carrier family with EF-hand Ca(2+)-binding motifs in their N-terminal domains. Both proteins and their C-terminal domains were overexpressed in Escherichia coli, reconstituted into liposomes and shown to catalyze the electrogenic exchange of aspartate for glutamate and a H(+). Overexpression of the carriers in transfected human cells increased the activity of the malate/aspartate NADH shuttle. These results demonstrate that citrin and aralar1 are isoforms of the hitherto unidentified aspartate/glutamate carrier and explain why mutations in citrin cause type II citrullinemia in humans. The activity of citrin and aralar1 as aspartate/glutamate exchangers was stimulated by Ca(2+) on the external side of the inner mitochondrial membrane, where the Ca(2+)-binding domains of these proteins are localized. These results show that the aspartate/glutamate carrier is regulated by Ca(2+) through a mechanism independent of Ca(2+) entry into mitochondria, and suggest a novel mechanism of Ca(2+) regulation of the aspartate/malate shuttle. << Less

  EMBO J. 20:5060-5069(2001) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• The mitochondrial aspartate/glutamate carrier (AGC or Aralar1) isoforms in D. melanogaster: biochemical characterization, gene structure, and evolutionary analysis.

  Lunetti P., Marsano R.M., Curcio R., Dolce V., Fiermonte G., Cappello A.R., Marra F., Moschetti R., Li Y., Aiello D., Del Arco Martinez A., Lauria G., De Leonardis F., Ferramosca A., Zara V., Capobianco L.

  <h4>Background</h4>In man two mitochondrial aspartate/glutamate carrier (AGC) isoforms, known as aralar and citrin, are required to accomplish several metabolic pathways. In order to fill the existing gap of knowledge in Drosophila melanogaster, we have studied aralar1 gene, orthologue of human AG ... >> More

  <h4>Background</h4>In man two mitochondrial aspartate/glutamate carrier (AGC) isoforms, known as aralar and citrin, are required to accomplish several metabolic pathways. In order to fill the existing gap of knowledge in Drosophila melanogaster, we have studied aralar1 gene, orthologue of human AGC-encoding genes in this organism.<h4>Methods</h4>The blastp algorithm and the "reciprocal best hit" approach have been used to identify the human orthologue of AGCs in Drosophilidae and non-Drosophilidae. Aralar1 proteins have been overexpressed in Escherichia coli and functionally reconstituted into liposomes for transport assays.<h4>Results</h4>The transcriptional organization of aralar1 comprises six isoforms, three constitutively expressed (aralar1-RA, RD and RF), and the remaining three distributed during the development or in different tissues (aralar1-RB, RC and RE). Aralar1-PA and Aralar1-PE, representative of all isoforms, have been biochemically characterized. Recombinant Aralar1-PA and Aralar1-PE proteins share similar efficiency to exchange glutamate against aspartate, and same substrate affinities than the human isoforms. Interestingly, although Aralar1-PA and Aralar1-PE diverge only in their EF-hand 8, they greatly differ in their specific activities and substrate specificity.<h4>Conclusions</h4>The tight regulation of aralar1 transcripts expression and the high request of aspartate and glutamate during early embryogenesis suggest a crucial role of Aralar1 in this Drosophila developmental stage. Furthermore, biochemical characterization and calcium sensitivity have identified Aralar1-PA and Aralar1-PE as the human aralar and citrin counterparts, respectively.<h4>General significance</h4>The functional characterization of the fruit fly mitochondrial AGC transporter represents a crucial step toward a complete understanding of the metabolic events acting during early embryogenesis. << Less

  Biochim. Biophys. Acta 1865:129854-129854(2021) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Electrogenic characteristics of the mitochondrial glutamate-aspartate antiporter.

  LaNoue K.F., Tischler M.E.

  J. Biol. Chem. 249:7522-7528(1974) [PubMed] [EuropePMC]