Identification of the Mitochondrial Glutamate Transporter
Open accessAbstract
The mitochondrial carriers are a family of transport proteins in the inner membranes of mitochondria. They shuttle substrates, metabolites, and cofactors through this membrane and connect cytoplasm functions with others in the matrix. Glutamate is co-transported with H(+) (or exchanged for OH(-)), but no protein has ever been associated with this activity. Two human expressed sequence tags encode proteins of 323 and 315 amino acids with 63% identity that are related to the aspartate-glutamate carrier, a member of the carrier family. They have been overexpressed in Escherichia coli and reconstituted into phospholipid vesicles. Their transport properties demonstrate that the two proteins are isoforms of the glutamate/H(+) symporter described in the past in whole mitochondria. Isoform 1 is expressed at higher levels than isoform 2 in all the tissues except in brain, where the two isoforms are expressed at comparable levels. The differences in expression levels and kinetic parameters of the two isoforms suggest that isoform 2 matches the basic requirement of all tissues especially with respect to amino acid degradation, and isoform 1 becomes operative to accommodate higher demands associated with specific metabolic functions such as ureogenesis.
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Glutamic acid targets SLC25A18, a glutamate transporter involved in excitatory signaling in neurons.
“Glutamic acid (DB00142) targets SLC25A18, a glutamate transporter86 and is involved in excitatory signaling in neurons87.”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [86]
The Discussion (page unavailable) identifies GC1 and GC2 as mitochondrial glutamate carriers, and the substrate-specificity results show that both transport L-glutamate. Our copy does not explicitly identify either isoform as SLC25A18, so it does not fully establish the named target. The neuronal-signaling clause has a separate citation (87) and is not attributed to this source. (LLM, conf=0.78)
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The human gene <i>SLC25A17</i> encodes a peroxisomal transporter of coenzyme A, FAD and NAD+
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Self-citationWestern, D., Timsina, J., Wang, L., Wang, C., Yang, C., Phillips, B., Wang, Y., Liu, M., Ali, M., Beric, A., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01972-8 · Cited by 111 · see citing works
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- Authors
- Fiermonte, G., Palmieri, L., Todisco, S., Agrimi, G., Palmieri, F., & Walker, J. E.
- Affiliations
- University of Bari Aldo Moro (IT)
- MRC Mitochondrial Biology Unit (GB)
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 277
- Issue
- 22
- Pages
- 19289-19294
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2052563744
- Cited by
- 216
- References
- 0
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 13 · 2023: 8 · 2022: 11 · 2021: 20 · 2020: 17 · 2019: 11 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 7 · 2013: 9 · 2012: 11
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Basilicata) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by)
- Funders
- Consiglio Nazionale delle Ricerche
- European Social Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- mitochondrial carrier protein, glutamate uptake, aspartate/glutamate carrier, protein isoforms, expressed sequence tags, recombinant protein expression, phospholipid vesicles, tissue expression, amino acid catabolism, ureogenesis, inner mitochondrial membrane
- MeSH terms
- Biological Transport, Brain, Cytoplasm, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Humans, Hydrogen, Hydrogen-Ion Concentration, Kinetics, Mitochondria, Molecular Sequence Data, Plasmids, Time Factors, Tissue Distribution, Polymerase Chain Reaction, Protein Isoforms, Expressed Sequence Tags, Mitochondrial Proteins, Membrane Transport Proteins, Amino Acid Transport System X-AG, Mitochondrial Membrane Transport Proteins
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