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- Title
Citrin and aralar1 are Ca<sup>2+</sup>-stimulated aspartate/glutamate transporters in mitochondria.
- Authors
Palmieri, L.; Pardo, B.; Lasorsa, F. M.; del Arco, A.; Kobayashi, K.; Iijima, M.; Runswick, M. J.; Walker, J. E.; Saheki, T.; Satrüstegui, J.; Palmieri, F.
- Abstract
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 Ca2+-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 Ca2+ on the external side of the inner mitochondrial membrane, where the Ca2+-binding domains of these proteins are localized. These results show that the aspartate/glutamate carrier is regulated by Ca2+ through a mechanism independent of Ca2+ entry into mitochondria, and suggest a novel mechanism of Ca2+ regulation of the aspartate/malate shuttle.
- Publication
EMBO Journal, 2001, Vol 20, Issue 18, p5060
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/20.18.5060