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

TitleCitrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria.
Publication TypeJournal Article
Year of Publication2001
AuthorsPalmieri, L, Pardo, B, Lasorsa, FM, del Arco, A, Kobayashi, K, Iijima, M, Runswick, MJ, Walker, JE, Saheki, T, Satrústegui, J, Palmieri, F
JournalEMBO J
Volume20
Issue18
Pagination5060-9
Date Published2001 Sep 17
ISSN0261-4189
KeywordsAmino Acid Transport Systems, Acidic, Antiporters, Calcium, Calcium-Binding Proteins, Carrier Proteins, Cell Line, Citrullinemia, Escherichia coli, Humans, Kinetics, Membrane Transport Proteins, Mitochondria, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, Models, Chemical, Organic Anion Transporters, Proteolipids, Transfection
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 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.

DOI10.1093/emboj/20.18.5060
Alternate JournalEMBO J.
Citation Key10.1093/emboj/20.18.5060
PubMed ID11566871
PubMed Central IDPMC125626