ArticleThe EMBO journal2001
Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers.
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Who cites it
219 citing papers in PubMed, 499 citations in OpenAlex.
- Mitochondrial calcium and ROS: present understanding and future directions.Mitochondrion · 2026Article
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Endothelial SLC25A13 links glutamine metabolism to angiogenesis.EMBO molecular medicine · 2026Article
- Redox coupling of lactate and β-hydroxybutyrate: An inter-organ circuit linking metabolic flexibility, mitochondrial adaptation, and disease.Redox biology · 2026Review
- Recurrent Hyperammonemic Encephalopathy in Adults with Citrin Deficiency: A Case Report of Two Genetically Confirmed Cases.Journal of clinical medicine · 2026Article
- The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes.The FEBS journal · 2026Article
- Presenilin-1 controls glycolysis and identity of pancreatic beta cells.Communications biology · 2026Article
- A transport-independent role for SLC25A12 in mitochondrial stress signalling.Nature cell biology · 2026Article
- Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.Biomolecules · 2026Review
- An inherited SLC25A12-related recessive form of congenital porencephaly in Limousin cattle.Genetics, selection, evolution : GSE · 2026Article
- The pyruvate generator is a common phenomenon in mitochondria from different rat and mouse brain regions.FEBS letters · 2026Article
- Aspartate-Glutamate Carrier 1 (International journal of molecular sciences · 2026Review
- When calcium calls the shots in FAD-dependent respiration.Nature metabolism · 2026Article
- From the cytosol to the inner membrane: biogenesis of the mitochondrial carrier family.Protein science : a publication of the Protein Society · 2026Review
- Aspartate availability drives differential engagement of the malate-aspartate shuttle.Molecular cell · 2026Article
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- SLC25A mitochondrial carriers as biomarkers and therapeutic targets of spaceflight-induced dysfunction: the ADP/ATP carrier (AAC3) as a structural case study.Journal of translational medicine · 2025Article
- Combined ketone body and glutamine supplementation restores aerobic energy production in AGC1-deficient neuronal progenitors.Cell death & disease · 2025Article
- WSSV-induced reversal of the malate-aspartate shuttle facilitates viral replication in shrimp hemocytes.Cell communication and signaling : CCS · 2025Article
- Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency.Nature metabolism · 2025Article
159 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.