{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:50:18Z","timestamp":1791978618485,"version":"4.4.0"},"reference-count":143,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007030","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["SAF2017-82560R"],"award-info":[{"award-number":["SAF2017-82560R"]}],"id":[{"id":"10.13039\/501100007030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>AGC1\/Aralar\/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal mitochondria. The deficiency in AGC1\/Aralar leads to the human rare disease named \u201cearly infantile epileptic encephalopathy 39\u201d (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and N-acetylaspartate (NAA). Current evidence suggest that neurons are the main brain cell type expressing Aralar. However, paradoxically, glial functions such as myelin and Glutamine (Gln) synthesis are markedly impaired in AGC1 deficiency. Herein, we discuss the role of the AGC1\/Aralar-MAS pathway in neuronal functions such as Asp and NAA synthesis, lactate use, respiration on glucose, glutamate (Glu) oxidation and other neurometabolic aspects. The possible mechanism triggering the pathophysiological findings in AGC1 deficiency, such as epilepsy and postnatal hypomyelination observed in humans and mice, are also included. Many of these mechanisms arise from findings in the aralar-KO mice model that extensively recapitulate the human disease including the astroglial failure to synthesize Gln and the dopamine (DA) mishandling in the nigrostriatal system. Epilepsy and DA mishandling are a direct consequence of the metabolic defect in neurons due to AGC1\/Aralar deficiency. However, the deficits in myelin and Gln synthesis may be a consequence of neuronal affectation or a direct effect of AGC1\/Aralar deficiency in glial cells. Further research is needed to clarify this question and delineate the transcellular metabolic fluxes that control brain functions. Finally, we discuss therapeutic approaches successfully used in AGC1-deficient patients and mice.<\/jats:p>","DOI":"10.3390\/ijms23010528","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Beatriz","family":"Pardo","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Universidad Aut\u00f3noma de Madrid (UAM)-Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"},{"name":"Instituto de Investigaciones Sanitarias Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Herrada-Soler","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Universidad Aut\u00f3noma de Madrid (UAM)-Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"},{"name":"Instituto de Investigaciones Sanitarias Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-2667","authenticated-orcid":false,"given":"Jorgina","family":"Satr\u00fastegui","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Universidad Aut\u00f3noma de Madrid (UAM)-Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"},{"name":"Instituto de Investigaciones Sanitarias Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-4942","authenticated-orcid":false,"given":"Laura","family":"Contreras","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Universidad Aut\u00f3noma de Madrid (UAM)-Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"},{"name":"Instituto de Investigaciones Sanitarias Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araceli","family":"del Arco","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Universidad Aut\u00f3noma de Madrid (UAM)-Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"},{"name":"Instituto de Investigaciones Sanitarias Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro Regional de Investigaciones Biom\u00e9dicas, Facultad de Ciencias Ambientales y Bioqu\u00edmica, Universidad de Castilla La Mancha, 45071 Toledo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0968-0004(79)90417-1","article-title":"Oxidation of cytosolic NADH formed during aerobic metabolism in mammalian cells","volume":"4","author":"Dawson","year":"1979","journal-title":"Trends Biochem. Sci."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"5060","DOI":"10.1093\/emboj\/20.18.5060","article-title":"Citrin and aralar1 are Ca2+-stimulated aspartate\/glutamate transporters in mitochondria","volume":"20","author":"Palmieri","year":"2001","journal-title":"EMBO J."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1046\/j.1432-1033.2002.03018.x","article-title":"Expression of the aspartate\/glutamate mitochondrial carriers aralar1 and citrin development and in adult rat tissues","volume":"269","author":"Morcillo","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0165-3806(03)00097-X","article-title":"Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord","volume":"143","author":"Ramos","year":"2003","journal-title":"Dev. Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/jcbfm.2010.146","article-title":"Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation","volume":"31","author":"Pardo","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_8","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_9","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_10","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_11","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":"4","author":"Falk","year":"2014","journal-title":"JIMD Reports"},{"key":"ref_12","first-page":"1234","article-title":"Dystonia-spasticity in a patient with a novel SLC25A12 mutation","volume":"30","author":"Parnes","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12967-016-0930-9","article-title":"New perspective in diagnostics of mitochondrial disorders: Two years\u00b4experience with whole-eexome sequencing at a national paediatric centre","volume":"14","author":"Pronicka","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1002\/ajmg.a.61322","article-title":"Longitudinal MRI findings in patient with SLC25A12 pathogenic variants inform disease progression and classification","volume":"179","author":"Kavanaugh","year":"2019","journal-title":"Am. J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.seizure.2019.04.018","article-title":"The landscape of early infantile epileptic encephalopathy in a consanguineous population","volume":"69","author":"Nashabat","year":"2019","journal-title":"Seizure Europ. J. Epilepsy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1055\/s-0039-3400976","article-title":"Expanding Phenotypic Spectrum of Cerebral Aspartate-Glutamate Carrier Isoform 1 (AGC1) Deficiency","volume":"51","author":"Pfeiffer","year":"2020","journal-title":"Neuropediatrics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"973","DOI":"10.3923\/pjbs.2020.973.976","article-title":"A novel nonsense gene variant responsible for early infantile epileptic encephalopathy type 39: Case report","volume":"23","author":"Saleh","year":"2020","journal-title":"Pak. J. Biol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1515\/jpem-2020-0410","article-title":"The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and refelctions on clinical spectrum","volume":"34","author":"Kose","year":"2021","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/jcbfm.2011.129","article-title":"Altered postnatal development of cortico-hippocampal neuronal electric activity in mice deficient for the mitochondrial aspartate-glutamate transporter","volume":"32","author":"Makarova","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/jnc.12096","article-title":"AGC1-malate aspartate shuttle activity is critical for dopamine handling in the nigrostriatal pathway","volume":"124","author":"Contreras","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1002\/jnr.22639","article-title":"Deficiency of the mitochondrial transporter of aspartate\/glutamate aralar\/AGC1 causes hypomyelination and neuronal defects unrelated to myelin deficits in mouse brain","volume":"89","author":"Ramos","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1002\/jnr.21500","article-title":"Mitochondrial transport proteins of the brain","volume":"85","author":"Berkich","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.neuron.2007.05.004","article-title":"Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons","volume":"24","author":"Xu","year":"2007","journal-title":"Neuron."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1152\/physrev.00005.2006","article-title":"Mitochondrial transporters as novel targets for intracellular calcium signaling","volume":"87","author":"Pardo","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1074\/jbc.M507270200","article-title":"Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria","volume":"281","author":"Pardo","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1523\/JNEUROSCI.3691-15.2016","article-title":"L-Lactate-Mediated Neuroprotection against Glutamate-Induced Excitotoxicity Requires ARALAR\/AGC1","volume":"36","author":"Rueda","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13957","DOI":"10.1523\/JNEUROSCI.0929-13.2013","article-title":"Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR\/AGC1-malate aspartate shuttle in intact cortical neurons","volume":"33","author":"Rueda","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e176","DOI":"10.1111\/epi.13193","article-title":"The ketogenic diet compensates for AGC1 deficiency and improves myelination","volume":"56","author":"Dahlin","year":"2015","journal-title":"Epilepsia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9293","DOI":"10.1523\/JNEUROSCI.0711-20.2020","article-title":"\u03b2OHB protective pathways in Aralar-KO neurons and brain: An alternative to ketogenic diet","volume":"40","author":"Casarejos","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41586-020-2741-7","article-title":"SLC25A51 is a mammalian mitochondrial NAD+ transporter","volume":"588","author":"Luongo","year":"2020","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0021-9258(18)56077-4","article-title":"Phosphorylation coupled to oxidation of dihydrophosphopyridine nucleotide","volume":"190","author":"Lehninger","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1016\/S0021-9258(19)61739-4","article-title":"The relation between intra- and extramitochondrial pyridine nucleotides","volume":"236","author":"Purvis","year":"1961","journal-title":"J. Biol. Chem."},{"key":"ref_33","unstructured":"Borst, P. (1963). Interrelations between Cytoplasmic and Mitochondrial Diphosphopyridine Nucleotide in Ehrlich Ascites Tumour Cells, Pergamon Press."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.cmet.2021.06.013","article-title":"Glycerol-3-phosphate biosynthesis regenerates cytosolic NAD + to alleviate mitochondrial disease","volume":"33","author":"Liu","year":"2021","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1126\/science.283.5404.981","article-title":"Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion","volume":"283","author":"Eto","year":"1999","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/978-1-4614-1788-0_29","article-title":"Redox shuttles in the brain","volume":"Volume 4","author":"Choi","year":"2012","journal-title":"Advances in Neurobiology. Neuronal Metabolism In Vivo"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1523\/JNEUROSCI.4178-07.2008","article-title":"A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function","volume":"28","author":"Cahoy","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/jnc.14047","article-title":"ARALAR\/AGC1 deficiency, a neurodevelopmental disorder with severe impairment of neuronal mitochondrial respiration, does not produce a primary increase in brain lactate","volume":"142","author":"Juaristi","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7522","DOI":"10.1016\/S0021-9258(19)81269-3","article-title":"Electrogenic characteristics of the mitochondrial glutamate-aspartate antiporter","volume":"249","author":"LaNoue","year":"1974","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000015595","article-title":"Assignement of the calcium-binding mitochondrial carrier Aralar1 gene (SLC25A12) to human chromosome band 2q31 by in situ hybridization","volume":"89","author":"Sanz","year":"2000","journal-title":"Cytogenet Cell Genet"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1006\/geno.1999.6006","article-title":"Genomic structure of the adult-onset type II citrullinemia gene, SLC25A13, and cloning and expression of its mouse homologue","volume":"62","author":"Sinasac","year":"1999","journal-title":"Genomics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1146\/annurev.bi.48.070179.004255","article-title":"Metabolite transport in mitochondria","volume":"48","author":"LaNoue","year":"1979","journal-title":"Annu. Rev. Biochem."},{"key":"ref_43","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_44","first-page":"328","article-title":"Failure to thrive and dyslipidemia caused by citrin deficiency: A novel clinical phenotype","volume":"11","author":"Song","year":"2009","journal-title":"Chin. J. Contemp. Pediatrics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Saheki, T., Moriyama, M., Funahashi, A., and Kuroda, E. (2020). AGC2 (Citrin) deficiency- From Recognition of the Disease till Construction of Therapeutic Procedures. Biomolecules, 10.","DOI":"10.3390\/biom10081100"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24701","DOI":"10.1074\/jbc.M401417200","article-title":"Identification of a novel human subfamioy of mitochondrial carriers with calcium-binding domains","volume":"279","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"30722","DOI":"10.1074\/jbc.M400445200","article-title":"Identification of the mitochondrial ATP-Mg\/Pi transporter: Bacterial expression, reconstitution, functional characterization, and tissue distribution","volume":"279","author":"Fiermonte","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7091","DOI":"10.1074\/jbc.M808066200","article-title":"Calcium signaling in brain mitochondria: Interplay of malate aspartate NADH shuttle and calcium uniporter\/mitochondrial dehydrogenase pathways","volume":"284","author":"Contreras","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.bbabio.2015.07.002","article-title":"Calcium-induced conformational changes in the regulatory domain of the human mitochondrial ATP-Mg\/Pi carrier","volume":"1847","author":"Harborne","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_50","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_51","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_52","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.tibs.2019.11.001","article-title":"The SLC25 mitochondrial carrier family: Structure and mechanism","volume":"45","author":"Ruprecht","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1146\/annurev-biochem-072820-020508","article-title":"Structural Mechanism of Transport of Mitochondrial Carriers","volume":"90","author":"Ruprecht","year":"2021","journal-title":"Annu. Rev. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.bbabio.2006.03.021","article-title":"The conserved substrate binding site of mitochondrial carriers","volume":"1757","author":"Kunji","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_55","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":"Nature Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/jnr.22283","article-title":"Low Levels of Citrin (SLC25A13) Expression in Adult Mouse Brain Restricted to Neuronal Clusters","volume":"88","author":"Contreras","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12255","DOI":"10.1523\/JNEUROSCI.3404-07.2007","article-title":"The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex","volume":"27","author":"Lovatt","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.neuint.2012.09.009","article-title":"Aralar mRNA and protein levels in neurons and astrocytes freshly isolated from young and adult mouse brain and in maturing cultured astrocytes","volume":"61","author":"Li","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"The Tabula Muris Consortium (2018). Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature, 562, 367\u2013372.","DOI":"10.1038\/s41586-018-0590-4"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.biopsych.2009.08.042","article-title":"Slc25a12 disruption alters myelination and neurofilaments: A model for hypomyelination syndrome and childhood neurodevelopment disorders","volume":"67","author":"Sakurai","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1113\/JP270254","article-title":"The regulation of neuronal mitochondrial metabolism by calcium","volume":"593","author":"Rueda","year":"2015","journal-title":"J. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/j.bbabio.2014.04.010","article-title":"Ca(2+) regulation of mitochondrial function in neurons","volume":"1837","author":"Rueda","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.bbabio.2016.04.003","article-title":"Glutamate excitotoxicity and Ca2+-regulation of respiration: Role of the Ca2+ activated mitochondrial transporters (CaMCs)","volume":"1857","author":"Rueda","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1038\/s41593-020-0689-4","article-title":"A glycolytic shift in Schwann cells supports injured axons","volume":"23","author":"Babetto","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e69438","DOI":"10.7554\/eLife.69438","article-title":"Glycolytic preconditioning in astrocytes mitigates trauma-induced neurodegeneration","volume":"10","author":"Metang","year":"2021","journal-title":"Elife"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e140521","DOI":"10.1172\/JCI140521","article-title":"Tanycytic networks mediate energy balance by feeding lactate to glucose-insensitive POMC neurons","volume":"131","author":"Lhomme","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.cell.2016.07.040","article-title":"Absolute quantification of matrix metabolites reveals the dynamics of mitochondrial metabolism","volume":"166","author":"Chen","year":"2016","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1471-4159.1992.tb08875.x","article-title":"Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytes in vitro","volume":"59","author":"Urenjak","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.1523\/JNEUROSCI.0894-18.2019","article-title":"Deletion of Neuronal GLT-1 in Mice Reveals Its Role in Synaptic Glutamate Homeostasis and Mitochondrial Function","volume":"39","author":"McNair","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1007\/s11064-020-03000-7","article-title":"Conditional Knockout of GLT-1 in Neurons Leads to Alterations in Aspartate Homeostasis and Synaptic Mitochondrial Metabolism in Striatum and Hippocampus","volume":"45","author":"McNair","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"108719","DOI":"10.1016\/j.neuropharm.2021.108719","article-title":"Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration","volume":"196","author":"Andersen","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.yjmcc.2004.04.008","article-title":"Localization and function of the brain excitatory amino acid transporter type 1 in cardiac mitochondria","volume":"37","author":"Ralphe","year":"2004","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"102160","DOI":"10.1016\/j.ceca.2020.102160","article-title":"NCX and EAAT transporters in ischemia: At the crossroad between glutamate metabolism and cell survival","volume":"86","author":"Piccirillo","year":"2020","journal-title":"Cell Calcium"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1074\/jbc.M610491200","article-title":"Ca2+ activation kinetics of the two aspartate-glutamate mitochondrial carriers, aralar and citrin: Role in the heart malate-aspartate NADH shuttle","volume":"282","author":"Contreras","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41586-019-1311-3","article-title":"Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function","volume":"571","author":"Bailis","year":"2019","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/glia.23574","article-title":"Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes","volume":"67","author":"Juaristi","year":"2019","journal-title":"Glia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1007\/s11064-019-02803-7","article-title":"The Response to Stimulation in Neurons and Astrocytes","volume":"44","author":"Juaristi","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1111\/j.1471-4159.1983.tb00849.x","article-title":"Pyruvate carboxylase activity in primary cultures of astrocytes and neurons","volume":"41","author":"Yu","year":"1983","journal-title":"J. Neurochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"646291","DOI":"10.3389\/fnins.2021.646291","article-title":"Glutamate Dehydrogenase Is Important for Ammonia Fixation and Amino Acid Homeostasis in Brain During Hyperammonemia","volume":"15","author":"Voss","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.neuint.2012.04.014","article-title":"siRNA knock down of glutamate dehydrogenase in astrocytes affects glutamate metabolism leading to extensive accumulation of the neuroactive amino acids glutamate and aspartate","volume":"61","author":"Skytt","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Hertz, L., and Rothman, D.L. (2017). Glutamine-Glutamate Cycle Flux Is Similar in Cultured Astrocytes and Brain and Both Glutamate Production and Oxidation Are Mainly Catalyzed by Aspartate Aminotransferase. Biology, 6.","DOI":"10.3390\/biology6010017"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"15579","DOI":"10.1073\/pnas.1412441111","article-title":"Pyruvate kinase and aspartate-glutamate carrier distributions reveal key metabolic links between neurons and glia in retina","volume":"111","author":"Lindsay","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.neuint.2015.04.001","article-title":"Role of AGC1\/aralar in the metabolic synergies between neuron and glia","volume":"88","author":"Contreras","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000111351","article-title":"Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: Differences revealed using aminooxyacetate","volume":"15","author":"McKenna","year":"1993","journal-title":"Dev. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1002\/glia.22895","article-title":"Dysfunctional TCA-cycle metabolism in glutamate dehydrogenase deficient astrocytes","volume":"63","author":"Nissen","year":"2015","journal-title":"Glia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1177\/0271678X17714680","article-title":"Glutamate dehydrogenase is essential to sustain neuronal oxidative energy metabolism during stimulation","volume":"38","author":"Hohnholt","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"27414","DOI":"10.1016\/S0021-9258(18)47001-9","article-title":"Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate\/aspartate shuttle","volume":"269","author":"Yudkoff","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2174\/157340608784872235","article-title":"Truncation of the Krebs cycle during hypoglycemic coma","volume":"4","author":"Sutherland","year":"2008","journal-title":"Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"36129","DOI":"10.1074\/jbc.M113.507285","article-title":"Inhibition of mitochondrial pyruvate transport by zaprinast causes massive accumulation of aspartate at the expense of glutamate in the retina","volume":"288","author":"Du","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chembiol.2021.10.007","article-title":"Inhibition of glucose transport synergizes with chemical or genetic disruption of mitochondrial metabolism and suppresses TCA cycle-deficient tumors","volume":"29","author":"Olszewski","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"ref_92","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_93","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00018-013-1389-y","article-title":"Single-nucleotide evolution quantifies the importance of each site along the structure of mitochondrial carriers","volume":"71","author":"Pierri","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00401-017-1739-1","article-title":"Leukodystrophies: A proposed classification system based on pathological changes and pathogenetic mechanisms","volume":"134","author":"Bugiani","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1073\/pnas.0913668107","article-title":"E3 ubiquitin ligase APC\/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation","volume":"107","author":"Almeida","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"11929","DOI":"10.1523\/JNEUROSCI.1860-14.2014","article-title":"An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex","volume":"34","author":"Zhang","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ajhg.2016.11.014","article-title":"Mutations in MDH2, encoding a Krebs cycle enzyme, cause early-onset severe encephalopathy","volume":"100","author":"Gusic","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s00439-019-02063-z","article-title":"MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy","volume":"138","author":"Broeks","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_99","first-page":"1","article-title":"Bi-allelic GOT2 mutations cause a treatable malate-aspartate shuttle-related encephalopathy","volume":"105","author":"Ramos","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bcp.2005.10.011","article-title":"Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: Current evidence and pharmacological tools","volume":"71","author":"McKenna","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/ana.10311","article-title":"Imaging the metabolic footprint of Glut1 deficiency on the brain","volume":"52","author":"Pascual","year":"2002","journal-title":"Ann Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Sharma, S., and Prasad, A.N. (2017). Inborn Errors of Metabolism and Epilepsy: Current Understanding, Diagnosis, and Treatment Approaches. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071384"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"De la Rossa, A., Laporte, M.H., Astori, S., Marissal, T., Montessuit, S., Sheshadri, P., Ramos-Fern\u00e1ndez, E., Mendez, P., Khani, A., and Quairiaux, H. (2020). Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate 1 import deficiency. bioRxiv.","DOI":"10.1101\/2020.12.22.423903"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"6202","DOI":"10.1523\/JNEUROSCI.0805-04.2004","article-title":"Dual-gene, dual-cell type therapy against an ecitotoxic insult by bolstering neuroenergetics","volume":"24","author":"Bliss","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1006\/jmre.1998.1618","article-title":"In vivo quantitation of cerebral metabolite concentrations using natural abundance 13C MRS at 1.5 T","volume":"136","year":"1999","journal-title":"J. Magn. Reson."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrn2797","article-title":"Myelination and the trophic support of long axons","volume":"11","author":"Nave","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1242\/jcs.151043","article-title":"Myelination at a glance","volume":"127","author":"Snaidero","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/00001756-199103000-00005","article-title":"Immunohistochemical localization of N-acetylaspartate in rat brain","volume":"2","author":"Moffett","year":"1991","journal-title":"Neuroreport"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF01181604","article-title":"Differential distribution of N-acetylaspartylglutamate and N-acetylaspartate immunoreactivities in rat forebrain","volume":"24","author":"Moffett","year":"1995","journal-title":"J. Neurocytol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1046\/j.1471-4159.2000.0740254.x","article-title":"In vitro expression of N-acetyl-aspartate by oligodendrocytes: Implications for proton magnetic resonance spectroscopy signal in vivo","volume":"74","author":"Bhakoo","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"14501","DOI":"10.1523\/JNEUROSCI.1056-15.2015","article-title":"N-acetylaspartate synthase deficiency corrects the myelin phenotype in a Canavan disease mouse model but does not affect survival time","volume":"35","author":"Maier","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/ana.24392","article-title":"Ablating N-acetylaspartate prevents leukodystrophy in a Canavan disease model","volume":"77","author":"Guo","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_114","first-page":"413","article-title":"Suppresing N-acetyl-L-aspartate synthesis prevents loss of neurons in a murine model of Canavan leukodystrophy","volume":"37","author":"Sohn","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/ana.102","article-title":"Absence of N-acetylaspartate in the human brain: Impact on neurospectroscopy?","volume":"49","author":"Martin","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature11007","article-title":"Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity","volume":"485","author":"Supplie","year":"2012","journal-title":"Nature"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The glutamate\/GABA-glutamine cycle: Aspects of transport, neurotransmitter homeostasis and ammonia transfer","volume":"98","author":"Bak","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev.physiol.65.092101.142131","article-title":"In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: Implications for brain function","volume":"65","author":"Rothman","year":"2003","journal-title":"Annu. Rev. Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11011-007-9068-z","article-title":"Energy metabolism in brain cells: Effects of elevated ammonia concentrations","volume":"22","author":"Hertz","year":"2007","journal-title":"Metab. Brain Dis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/0006-8993(85)90552-9","article-title":"Pyruvate carboxylase: An astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools","volume":"329","author":"Shank","year":"1985","journal-title":"Brain Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.1528-1167.2008.01492.x","article-title":"Glutamate and astrocytes--key players in human mesial temporal lobe epilepsy?","volume":"49","author":"Eid","year":"2008","journal-title":"Epilepsia"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"6372","DOI":"10.1523\/JNEUROSCI.22-15-06372.2002","article-title":"A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy","volume":"22","author":"Sepkuty","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"8537","DOI":"10.1523\/JNEUROSCI.0329-06.2006","article-title":"Dynamic regulation of synaptic GABA release by the glutamate-glutamine cycle in hippocampal area CA1","volume":"26","author":"Liang","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.neuron.2008.04.002","article-title":"Astrocytes in the epileptic brain","volume":"58","author":"Wetherington","year":"2008","journal-title":"Neuron"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1087753","article-title":"Molecular pathways of neurodegeneration in Parkinson\u00b4s disease","volume":"302","author":"Dawson","year":"2003","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Zampese, E., and Surmeier, D.J. (2020). Calcium, Bioenergetics, and Parkinson\u00b4s disease. Cells, 9.","DOI":"10.3390\/cells9092045"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41586-021-04059-0","article-title":"Disruption of mitochondrial complex I induces progressive parkinsonism","volume":"599","author":"Zampese","year":"2021","journal-title":"Nature"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.yexcr.2017.03.002","article-title":"Food for thought: Impact of metabolism on neuronal excitability","volume":"360","author":"Alves","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.pediatrneurol.2007.03.009","article-title":"GLUT1 deficiency with delayed myelination responding to ketogenic diet","volume":"37","author":"Klepper","year":"2007","journal-title":"Pediatr. Neurol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1177\/0883073809337162","article-title":"Ketogenic diets: An update for child neurologists","volume":"24","author":"Kossoff","year":"2009","journal-title":"J. Child Neurol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/j.1469-8749.2008.03216.x","article-title":"The ketogenic diet improves recently worsened focal epilepsy","volume":"51","author":"Villeneuve","year":"2009","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1177\/0883073814531822","article-title":"Long-term clinical course of Glut1 deficiency syndrome","volume":"30","author":"Alter","year":"2015","journal-title":"J. Child Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.yebeh.2011.02.018","article-title":"Dietary therapies for epilepsy: Future research","volume":"22","author":"Kessler","year":"2011","journal-title":"Epilepsy Behav."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Vanderperre, B., Herzig, S., Krznar, P., H\u00f6rl, M., Ammar, Z., Montessuit, S., Pierredon, S., Zamboni, N., and Martinou, J.-C. (2016). Embryonic lethality of mitochondrial pyruvate carrier 1 deficient mouse can be rescued by a ketogenic diet. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006056"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.brainresrev.2008.09.002","article-title":"The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies","volume":"59","author":"Maalouf","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.tins.2012.11.005","article-title":"The ketogenic diet: Metabolic influences on brain excitability and epilepsy","volume":"36","author":"Lutas","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/ana.24424","article-title":"Ketone bodies mediate anti-seizure effects through mitochondrial permeability transition","volume":"78","author":"Kim","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1073\/pnas.97.10.5440","article-title":"D-beta- hydroxybutyrate protects neurons in models of Alzheimer\u00b4s and Parkinson\u00b4s disease","volume":"97","author":"Kashiwaya","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1172\/JCI200318797","article-title":"D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson\u2019s disease","volume":"112","author":"Tieu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1002\/jnr.21021","article-title":"D-\u03b2-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson\u2019s disease","volume":"84","author":"Imamura","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1471-4159.2007.05108.x","article-title":"VMAT2 and dopamine neuron loss in a primate model of Parkinson\u2019s disease","volume":"105","author":"Chen","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(63)91500-9","article-title":"The glucose fatty acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus","volume":"1","author":"Randle","year":"1963","journal-title":"Lancet"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1096\/fj.201500182","article-title":"Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems","volume":"30","author":"Thevenet","year":"2016","journal-title":"FASEB J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/528\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:36:06Z","timestamp":1760362566000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":143,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010528"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010528","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,4]]}}}