Details

Autor(en) / Beteiligte

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

Titel

Citrin and aralar1 are Ca2+-stimulated aspartate/glutamate transporters in mitochondria

Ist Teil von

• The EMBO journal, 2001-09, Vol.20 (18), p.5060-5069

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2001

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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.