{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:42:59Z","timestamp":1790800979137,"version":"4.1.0"},"reference-count":110,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Members of the mitochondrial carrier (MC) protein family transport various molecules across the mitochondrial inner membrane to interlink steps of metabolic pathways and biochemical processes that take place in different compartments; i.e., are localized partly inside and outside the mitochondrial matrix. MC substrates consist of metabolites, inorganic anions (such as phosphate and sulfate), nucleotides, cofactors and amino acids. These compounds have been identified by in vitro transport assays based on the uptake of radioactively labeled substrates into liposomes reconstituted with recombinant purified MCs. By using this approach, 18 human, plant and yeast MCs for amino acids have been characterized and shown to transport aspartate, glutamate, ornithine, arginine, lysine, histidine, citrulline and glycine with varying substrate specificities, kinetics, influences of the pH gradient, and capacities for the antiport and uniport mode of transport. Aside from providing amino acids for mitochondrial translation, the transport reactions catalyzed by these MCs are crucial in energy, nitrogen, nucleotide and amino acid metabolism. In this review we dissect the transport properties, phylogeny, regulation and expression levels in different tissues of MCs for amino acids, and summarize the main structural aspects known until now about MCs. The effects of their disease-causing mutations and manipulation of their expression levels in cells are also considered as clues for understanding their physiological functions.<\/jats:p>","DOI":"10.3390\/ijms20184456","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T10:52:26Z","timestamp":1568112746000},"page":"4456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Mitochondrial Carriers for Aspartate, Glutamate and Other Amino Acids: A Review"],"prefix":"10.3390","volume":"20","author":[{"given":"Magnus","family":"Monn\u00e9","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, Laboratory of Biochemistry and Molecular Biology, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"},{"name":"Department of Sciences, University of Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Vozza","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, Laboratory of Biochemistry and Molecular Biology, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"},{"name":"Center of Excellence in Comparative Genomics, University of Bari, via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Massimo","family":"Lasorsa","sequence":"additional","affiliation":[{"name":"CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Porcelli","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, Laboratory of Biochemistry and Molecular Biology, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, Laboratory of Biochemistry and Molecular Biology, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"},{"name":"Center of Excellence in Comparative Genomics, University of Bari, via Orabona 4, 70125 Bari, Italy"},{"name":"CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0167-7306(08)60184-2","article-title":"Metabolite carriers in mitochondria","volume":"Volume 23","author":"Ernster","year":"1992","journal-title":"Molecular Mechanisms in Bioenergetics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.mam.2012.05.005","article-title":"The mitochondrial transporter family SLC25: Identification, properties and physiopathology","volume":"34","author":"Palmieri","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/0014-5793(82)80648-0","article-title":"Internal sequence repeats and the path of polypeptide in mitochondrial ADP\/ATP translocase","volume":"144","author":"Saraste","year":"1982","journal-title":"FEBS Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/0014-5793(94)00329-7","article-title":"Mitochondrial carrier proteins","volume":"346","author":"Palmieri","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1042\/bse0470037","article-title":"Mitochondrial metabolite transport","volume":"47","author":"Palmieri","year":"2010","journal-title":"Essays Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1365-313X.2011.04516.x","article-title":"Evolution, structure and function of mitochondrial carriers: A review with new insights","volume":"66","author":"Palmieri","year":"2011","journal-title":"Plant J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.febslet.2009.10.063","article-title":"Structure and function of mitochondrial carriers - role of the transmembrane helix P and G residues in the gating and transport mechanism","volume":"584","author":"Palmieri","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1016\/j.bbamcr.2016.03.007","article-title":"Discoveries, metabolic roles and diseases of mitochondrial carriers: A review","volume":"1863","author":"Palmieri","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1042\/bj2940293","article-title":"Abundant bacterial expression and reconstitution of an intrinsic membrane-transport protein from bovine mitochondria","volume":"294","author":"Fiermonte","year":"1993","journal-title":"Biochem. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0076-6879(79)56029-7","article-title":"Direct methods for measuring metabolite transport and distribution in mitochondria","volume":"56","author":"Palmieri","year":"1979","journal-title":"Methods Enzymol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0076-6879(95)60150-3","article-title":"Mitochondrial metabolite carrier proteins: Purification, reconstitution, and transport studies","volume":"260","author":"Palmieri","year":"1995","journal-title":"Methods Enzymol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/B978-0-12-800223-0.00008-6","article-title":"Antiporters of the mitochondrial carrier family","volume":"73","author":"Palmieri","year":"2014","journal-title":"Curr. Top. Membr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nature02056","article-title":"Structure of mitochondrial ADP\/ATP carrier in complex with carboxyatractyloside","volume":"426","author":"Kahn","year":"2003","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E426","DOI":"10.1073\/pnas.1320692111","article-title":"Structures of yeast mitochondrial ADP\/ATP carriers support a domain-based alternating-access transport mechanism","volume":"111","author":"Ruprecht","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cell.2018.11.025","article-title":"The Molecular Mechanism of Transport by the Mitochondrial ADP\/ATP Carrier","volume":"176","author":"Ruprecht","year":"2019","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0968-0004(79)90215-9","article-title":"The ADP, ATP shuttle of the mitochondrion","volume":"4","author":"Klingenberg","year":"1979","journal-title":"Trends Biochem. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bbamem.2008.04.011","article-title":"The ADP and ATP transport in mitochondria and its carrier","volume":"1778","author":"Klingenberg","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8563","DOI":"10.1021\/bi050543r","article-title":"Ligand-protein interaction in biomembrane carriers. The induced transition fit of transport catalysis","volume":"44","author":"Klingenberg","year":"2005","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1073\/pnas.0509994103","article-title":"Mitochondrial carriers in the cytoplasmic state have a common substrate binding site","volume":"103","author":"Robinson","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"28445","DOI":"10.1074\/jbc.M804637200","article-title":"\u03b1-Isopropylmalate, a leucine biosynthesis intermediate in yeast, is transported by the mitochondrial oxalacetate carrier","volume":"283","author":"Marobbio","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0005-2736(94)90281-X","article-title":"The reconstituted carnitine carrier from rat liver mitochondria: Evidence for a transport mechanism different from that of the other mitochondrial translocators","volume":"1189","author":"Indiveri","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5060","DOI":"10.1093\/emboj\/20.18.5060","article-title":"Citrin and aralar1 are Ca(2+)-stimulated aspartate\/glutamate transporters in mitochondria","volume":"20","author":"Palmieri","year":"2001","journal-title":"EMBO J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"38686","DOI":"10.1074\/jbc.M304988200","article-title":"Recombinant expression of the Ca(2+)-sensitive aspartate\/glutamate carrier increases mitochondrial ATP production in agonist-stimulated Chinese hamster ovary cells","volume":"278","author":"Lasorsa","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1038\/ncomms6491","article-title":"Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate\/glutamate carriers","volume":"5","author":"Thangaratnarajah","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23327","DOI":"10.1074\/jbc.273.36.23327","article-title":"Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain","volume":"273","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/9667","article-title":"The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein","volume":"22","author":"Kobayashi","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1042\/bj3450725","article-title":"Characterization of a second member of the subfamily of calcium-binding mitochondrial carriers expressed in human non-excitable tissues","volume":"345","author":"Agudo","year":"2000","journal-title":"Biochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0065-2571(00)00022-4","article-title":"Pathogenesis of adult-onset type II citrullinemia caused by deficiency of citrin, a mitochondrial solute carrier protein: Tissue and subcellular localization of citrin","volume":"41","author":"Iijima","year":"2001","journal-title":"Adv. Enzyme Regul."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15979","DOI":"10.1016\/S0021-9258(18)47685-5","article-title":"Reconstitution of the malate\/aspartate shuttle from mitochondria","volume":"262","author":"Indiveri","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s00424-003-1099-7","article-title":"The mitochondrial transporter family (SLC25): Physiological and pathological implications","volume":"447","author":"Palmieri","year":"2004","journal-title":"Pfl\u00fcg. Arch."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1056\/NEJMoa0900591","article-title":"AGC1 deficiency associated with global cerebral hypomyelination","volume":"361","author":"Wibom","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/8904_2013_287","article-title":"AGC1 Deficiency Causes Infantile Epilepsy, Abnormal Myelination, and Reduced N-Acetylaspartate","volume":"14","author":"Falk","year":"2014","journal-title":"JIMD Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.bbadis.2017.02.022","article-title":"Down-regulation of the mitochondrial aspartate-glutamate carrier isoform 1 AGC1 inhibits proliferation and N-acetylaspartate synthesis in Neuro2A cells","volume":"1863","author":"Profilo","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"31333","DOI":"10.1074\/jbc.M505286200","article-title":"Reduced N-acetylaspartate levels in mice lacking aralar, a brain- and muscle-type mitochondrial aspartate-glutamate carrier","volume":"280","author":"Jalil","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Petralla, S., Pe\u00f1a-Altamira, L.E., Poeta, E., Massenzio, F., Virgili, M., Barile, S.N., Sbano, L., Profilo, E., Corricelli, M., and Danese, A. (2019). Deficiency of mitochondrial aspartate\/glutamate carrier 1 leads to oligodendrocyte precursor cell proliferation defects both in vitro and in vivo. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184486"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s10545-014-9708-5","article-title":"Mitochondrial transporters of the SLC25 family and associated diseases: A review","volume":"37","author":"Palmieri","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s100380200046","article-title":"Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD)","volume":"47","author":"Saheki","year":"2002","journal-title":"J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ymgme.2011.08.022","article-title":"A new Caucasian case of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD): A clinical, molecular, and functional study","volume":"104","author":"Fiermonte","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJMc0707353","article-title":"An adult with type 2 citrullinemia presenting in Europe","volume":"358","author":"Fiermonte","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2014.01.032","article-title":"Molecular genetics of citrullinemia types I and II","volume":"431","author":"Woo","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0167-4781(01)00376-1","article-title":"Expression of three mitochondrial solute carriers, citrin, aralar1 and ornithine transporter, in relation to urea cycle in mice","volume":"1574","author":"Begum","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Convertini, P., Todisco, S., De Santis, F., Pappalardo, I., Iacobazzi, D., Castiglione Morelli, M.A., Fondufe-Mittendorf, Y.N., Martelli, G., Palmieri, F., and Infantino, V. (2019). Transcriptional Regulation Factors of the Human Mitochondrial Aspartate\/Glutamate Carrier Gene, Isoform 2 (SLC25A13): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081888"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.biocel.2015.01.004","article-title":"The mitochondrial aspartate\/glutamate carrier isoform 1 gene expression is regulated by CREB in neuronal cells","volume":"60","author":"Menga","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.bbadis.2018.10.018","article-title":"Epigenetic upregulation and functional role of the mitochondrial aspartate\/glutamate carrier isoform 1 in hepatocellular carcinoma","volume":"1865","author":"Infantino","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1042\/BJ20090729","article-title":"Silencing of the mitochondrial NADH shuttle component aspartate-glutamate carrier AGC1\/Aralar1 in INS-1E cells and rat islets","volume":"424","author":"Casimir","year":"2009","journal-title":"Biochem. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1046\/j.1365-2958.2003.03742.x","article-title":"Identification and metabolic role of the mitochondrial aspartate-glutamate transporter in Saccharomyces cerevisiae","volume":"50","author":"Cavero","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ymgme.2017.07.004","article-title":"Three mitochondrial transporters of Saccharomyces cerevisiae are essential for ammonium fixation and lysine biosynthesis in synthetic minimal medium","volume":"122","author":"Scarcia","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s12210-018-0687-6","article-title":"In Saccharomyces cerevisiae grown in synthetic minimal medium supplemented with non-fermentable carbon sources glutamate is synthesized within mitochondria","volume":"29","author":"Scarcia","year":"2018","journal-title":"Rendiconti Lincei"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1074\/jbc.RA117.000771","article-title":"Uncoupling proteins 1 and 2 (UCP1 and UCP2) from Arabidopsis thaliana are mitochondrial transporters of aspartate, glutamate, and dicarboxylates","volume":"293","author":"Daddabbo","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19587","DOI":"10.1073\/pnas.0607751103","article-title":"Mitochondrial uncoupling protein is required for efficient photosynthesis","volume":"103","author":"Sweetlove","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19289","DOI":"10.1074\/jbc.M201572200","article-title":"Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms","volume":"277","author":"Fiermonte","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.bbabio.2013.07.002","article-title":"Mitochondrial glutamate carriers from Drosophila melanogaster: Biochemical, evolutionary and modeling studies","volume":"1827","author":"Lunetti","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"988S","DOI":"10.1093\/jn\/130.4.988S","article-title":"Glutamate, at the interface between amino acid and carbohydrate metabolism","volume":"130","author":"Brosnan","year":"2000","journal-title":"J. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"25004","DOI":"10.1074\/jbc.M109.015495","article-title":"Mitochondrial glutamate carrier GC1 as a newly identified player in the control of glucose-stimulated insulin secretion","volume":"284","author":"Casimir","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1086\/427564","article-title":"Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy","volume":"76","author":"Molinari","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1399-0004.2009.01236.x","article-title":"Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts","volume":"76","author":"Molinari","year":"2009","journal-title":"Clin. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/ana.23998","article-title":"SLC25A22 is a novel gene for migrating partial seizures in infancy","volume":"76","author":"Poduri","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lemattre, C., Imbert-Bouteille, M., Gatinois, V., Benit, P., Sanchez, E., Guignard, T., Tran Mau-Them, F., Haquet, E., Rivier, F., and Carme, E. (2019). Report on three additional patients and genotype-phenotype correlation in SLC25A22-related disorders group. Eur. J. Hum. Genet., in press.","DOI":"10.1038\/s41431-019-0433-2"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fncel.2017.00149","article-title":"Inhibition of the Mitochondrial Glutamate Carrier SLC25A22 in Astrocytes Leads to Intracellular Glutamate Accumulation","volume":"11","author":"Goubert","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.bbabio.2018.08.001","article-title":"Molecular identification and functional characterization of a novel glutamate transporter in yeast and plant mitochondria","volume":"1859","author":"Porcelli","year":"2018","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.abb.2005.07.016","article-title":"Mitochondrial transporters involved in oleic acid utilization and glutamate metabolism in yeast","volume":"442","author":"Trotter","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.molp.2015.09.005","article-title":"Amino Acid Catabolism in Plants","volume":"8","author":"Hildebrandt","year":"2015","journal-title":"Mol. Plant"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1111\/tpj.12082","article-title":"Arabidopsis A BOUT DE SOUFFLE is a putative mitochondrial transporter involved in photorespiratory metabolism and is required for meristem growth at ambient CO\u2082 levels","volume":"73","author":"Eisenhut","year":"2013","journal-title":"Plant J. Cell Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1002\/j.1460-2075.1985.tb04049.x","article-title":"The reconstituted isolated uncoupling protein is a membrane potential driven H+ translocator","volume":"4","author":"Klingenberg","year":"1985","journal-title":"EMBO J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.bbabio.2006.02.005","article-title":"The physiological regulation of uncoupling proteins","volume":"1757","author":"Nicholls","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/BJ20070867","article-title":"Molecular identification of three Arabidopsis thaliana mitochondrial dicarboxylate carrier isoforms: Organ distribution, bacterial expression, reconstitution into liposomes and functional characterization","volume":"410","author":"Palmieri","year":"2008","journal-title":"Biochem. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1073\/pnas.1317400111","article-title":"UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation","volume":"111","author":"Vozza","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.bbabio.2019.07.010","article-title":"The human uncoupling proteins 5 and 6 (UCP5\/SLC25A14 and UCP6\/SLC25A30) transport sulfur oxyanions, phosphate and dicarboxylates","volume":"1860","author":"Gorgoglione","year":"2019","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1096\/fj.07-8945com","article-title":"Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization","volume":"22","author":"Pecqueur","year":"2007","journal-title":"FASEB J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng0397-269","article-title":"Uncoupling protein-2: A novel gene linked to obesity and hyperinsulinemia","volume":"15","author":"Fleury","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Barroso, M.M., Giurgea, I., Bouillaud, F., Anedda, A., Bellann\u00e9-Chantelot, C., Hubert, L., de Keyzer, Y., de Lonlay, P., and Ricquier, D. (2008). Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion. PLoS One, 3.","DOI":"10.1371\/journal.pone.0003850"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1210\/jc.2016-3164","article-title":"Novel Hypoglycemia Phenotype in Congenital Hyperinsulinism Due to Dominant Mutations of Uncoupling Protein 2","volume":"102","author":"Ferrara","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/88911","article-title":"A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans","volume":"28","author":"Esterbauer","year":"2001","journal-title":"Nat Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/tra.12397","article-title":"Human Fumarate Hydratase Is Dual Localized by an Alternative Transcription Initiation Mechanism","volume":"17","author":"Dik","year":"2016","journal-title":"Traffic Cph. Den."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0014-5793(97)00630-3","article-title":"Identification of the yeast ARG-11 gene as a mitochondrial ornithine carrier involved in arginine biosynthesis","volume":"410","author":"Palmieri","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"25011","DOI":"10.1074\/jbc.271.40.25011","article-title":"The ARG11 gene of Saccharomyces cerevisiae encodes a mitochondrial integral membrane protein required for arginine biosynthesis","volume":"271","author":"Crabeel","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"32778","DOI":"10.1074\/jbc.M302317200","article-title":"The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms","volume":"278","author":"Fiermonte","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00726-015-2096-9","article-title":"Asymmetric dimethylarginine is transported by the mitochondrial carrier SLC25A2","volume":"48","author":"Porcelli","year":"2016","journal-title":"Amino Acids"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7925","DOI":"10.1074\/jbc.M111.324855","article-title":"Substrate specificity of the two mitochondrial ornithine carriers can be swapped by single mutation in substrate binding site","volume":"287","author":"Miniero","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1432-1033.1992.tb17070.x","article-title":"Identification and purification of the ornithine\/citrulline carrier from rat liver mitochondria","volume":"207","author":"Indiveri","year":"1992","journal-title":"Eur. J. Biochem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0005-2728(94)90048-5","article-title":"Kinetic characterization of the reconstituted ornithine carrier from rat liver mitochondria","volume":"1188","author":"Indiveri","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1042\/bj3270349","article-title":"The purified and reconstituted ornithine\/citrulline carrier from rat liver mitochondria: Electrical nature and coupling of the exchange reaction with H+ translocation","volume":"327","author":"Indiveri","year":"1997","journal-title":"Biochem. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0006-291X(02)00549-1","article-title":"Hormonal induction of hepatic mitochondrial ornithine\/citrulline transporter mRNA","volume":"294","author":"Morris","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3360001","article-title":"Arginine metabolism: Nitric oxide and beyond","volume":"336","author":"Wu","year":"1998","journal-title":"Biochem. J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1007\/s00726-015-1990-5","article-title":"Mitochondrial transporters for ornithine and related amino acids: A review","volume":"47","author":"Miniero","year":"2015","journal-title":"Amino Acids"},{"key":"ref_86","first-page":"761","article-title":"Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26","volume":"97","author":"Kishita","year":"2015","journal-title":"Am. J. Med. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5975","DOI":"10.1093\/emboj\/cdg574","article-title":"Identification and functional reconstitution of yeast mitochondrial carrier for S-adenosylmethionine","volume":"22","author":"Marobbio","year":"2003","journal-title":"EMBO J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1042\/bj20031664","article-title":"Identification of the human mitochondrial S-adenosylmethionine transporter: Bacterial expression, reconstitution, functional characterization and tissue distribution","volume":"379","author":"Agrimi","year":"2004","journal-title":"Biochem. J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1104\/pp.106.086975","article-title":"Molecular identification of an Arabidopsis S-adenosylmethionine transporter. Analysis of organ distribution, bacterial expression, reconstitution into liposomes, and functional characterization","volume":"142","author":"Palmieri","year":"2006","journal-title":"Plant Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/humu.20930","article-title":"Identification of novel mutations in the SLC25A15 gene in hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome: A clinical, molecular, and functional study","volume":"30","author":"Tessa","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ymgme.2014.03.002","article-title":"A novel mutation in the SLC25A15 gene in a Turkish patient with HHH syndrome: Functional analysis of the mutant protein","volume":"112","author":"Marobbio","year":"2014","journal-title":"Mol Genet Metab"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ymgme.2015.03.003","article-title":"Pathogenic potential of SLC25A15 mutations assessed by transport assays and complementation of Saccharomyces cerevisiae ORT1 null mutant","volume":"115","author":"Marobbio","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13023-015-0242-9","article-title":"The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome","volume":"10","author":"Martinelli","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"38796","DOI":"10.1074\/jbc.M306372200","article-title":"A novel mitochondrial carnitine-acylcarnitine translocase induced by partial hepatectomy and fasting","volume":"278","author":"Sekoguchi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1203\/PDR.0b013e3181a283c1","article-title":"The human and mouse SLC25A29 mitochondrial transporters rescue the deficient ornithine metabolism in fibroblasts of patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome","volume":"66","author":"Camacho","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13374","DOI":"10.1074\/jbc.M114.547448","article-title":"The human gene SLC25A29, of solute carrier family 25, encodes a mitochondrial transporter of basic amino acids","volume":"289","author":"Porcelli","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1042\/bj3440555","article-title":"Lysine degradation through the saccharopine pathway in mammals: Involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse","volume":"344","author":"Papes","year":"1999","journal-title":"Biochem. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1083\/jcb.201807204","article-title":"The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis","volume":"218","author":"Zhou","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fphys.2015.00020","article-title":"Nitric oxide and mitochondria in metabolic syndrome","volume":"6","author":"Litvinova","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.tips.2005.02.005","article-title":"Mitochondrial nitric oxide synthase","volume":"26","author":"Ghafourifar","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1046\/j.1365-313X.2003.01685.x","article-title":"Identification of a mitochondrial transporter for basic amino acids in Arabidopsis thaliana by functional reconstitution into liposomes and complementation in yeast","volume":"33","author":"Hoyos","year":"2003","journal-title":"Plant J."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Catoni, E., Desimone, M., Hilpert, M., Wipf, D., Kunze, R., Schneider, A., Fl\u00fcgge, U.-I., Schumacher, K., and Frommer, W.B. (2003). Expression pattern of a nuclear encoded mitochondrial arginine-ornithine translocator gene from Arabidopsis. BMC Plant Biol., 3.","DOI":"10.1186\/1471-2229-3-1"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.bbabio.2006.03.025","article-title":"Arabidopsis mitochondria have two basic amino acid transporters with partially overlapping specificities and differential expression in seedling development","volume":"1757","author":"Palmieri","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"330","DOI":"10.3389\/fpls.2014.00330","article-title":"Basic amino acid carrier 2 gene expression modulates arginine and urea content and stress recovery in Arabidopsis leaves","volume":"5","author":"Planchais","year":"2014","journal-title":"Front. Plant Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1104\/pp.109.152371","article-title":"Mutations in the hyperosmotic stress-responsive mitochondrial BASIC AMINO ACID CARRIER2 enhance proline accumulation in Arabidopsis","volume":"152","author":"Toka","year":"2010","journal-title":"Plant Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/ng.359","article-title":"Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia","volume":"41","author":"Guernsey","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"19746","DOI":"10.1074\/jbc.M116.736876","article-title":"Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia","volume":"291","author":"Lunetti","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Murray, J.P., Prykhozhij, S.V., Dufay, J.N., Steele, S.L., Gaston, D., Nasrallah, G.K., Coombs, A.J., Liwski, R.S., Fernandez, C.V., and Berman, J.N. (2016). Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005783"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"eaat9528","DOI":"10.1126\/science.aat9528","article-title":"SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism","volume":"362","author":"Kory","year":"2018","journal-title":"Science"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.cell.2009.08.005","article-title":"Importing mitochondrial proteins: Machineries and mechanisms","volume":"138","author":"Chacinska","year":"2009","journal-title":"Cell"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4456\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:18:22Z","timestamp":1760188702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,10]]},"references-count":110,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijms20184456"],"URL":"https:\/\/doi.org\/10.3390\/ijms20184456","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,10]]}}}