Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver

Satrústegui, 2007, Mitochondrial transporters as novel targets for intracellular calcium signaling, Physiol. Rev., 87, 29, 10.1152/physrev.00005.2006 Palmieri, 2001, Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria, EMBO J., 20, 5060, 10.1093/emboj/20.18.5060 del Arco, 1998, Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain, J. Biol. Chem., 273, 23327, 10.1074/jbc.273.36.23327 Kobayashi, 1999, The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein, Nat. Genet., 22, 159, 10.1038/9667 Del Arco, 2000, Characterization of a second member of the subfamily of calcium-binding mitochondrial carriers expressed in human non-excitable tissues, Biochem. J., 345, 725, 10.1042/bj3450725 Borst, 2020, The malate-aspartate shuttle (Borst cycle): how it started and developed into a major metabolic pathway, IUBMB Life, 72, 2241, 10.1002/iub.2367 Sullivan, 2015, Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells, Cell., 162, 552, 10.1016/j.cell.2015.07.017 Jalil, 2005, Reduced N-acetylaspartate levels in mice lacking aralar, a brain- and muscle-type mitochondrial aspartate-glutamate carrier, J. Biol. Chem., 280, 31333, 10.1074/jbc.M505286200 Pardo, 2011, Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation, J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab., 31, 90, 10.1038/jcbfm.2010.146 Saheki, 2020, AGC2 (citrin) deficiency-from recognition of the disease till construction of therapeutic procedures, Biomolecules., 10, E1100, 10.3390/biom10081100 del Arco, 2002, Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissues, Eur. J. Biochem., 269, 3313, 10.1046/j.1432-1033.2002.03018.x Ramos, 2003, Developmental changes in the Ca2+−regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord, Brain Res. Dev. Brain Res., 143, 33, 10.1016/S0165-3806(03)00097-X Iijima, 2001, Pathogenesis of adult-onset type II citrullinemia caused by deficiency of citrin, a mitochondrial solute carrier protein: tissue and subcellular localization of citrin, Adv. Enzym. Regul., 41, 325, 10.1016/S0065-2571(00)00022-4 Saheki, 2005, Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate–glutamate carrier, Hepatol. Res., 4 Okano, 2019, Current treatment for citrin deficiency during NICCD and adaptation/compensation stages_ strategy to prevent CTLN2, Mol. Genet. Metab., 127, 175, 10.1016/j.ymgme.2019.06.004 Kido, 2022, Clinical manifestation and long-term outcome of citrin deficiency: report from a nationwide study in Japan, J. Inherit. Metab. Dis., 10.1002/jimd.12483 Saheki, 2010, Citrin deficiency and current treatment concepts, Mol. Genet. Metab., 6 Bočkor, 2017, Repeated AAV-mediated gene transfer by serotype switching enables long-lasting therapeutic levels of hUgt1a1 enzyme in a mouse model of Crigler-Najjar syndrome type I, Gene Ther., 24, 649, 10.1038/gt.2017.75 Ledley, 1985, Gene transfer and expression of human phenylalanine hydroxylase, Science., 228, 77, 10.1126/science.3856322 Gonzalez-Aseguinolaza, 2011, Gene therapy of liver diseases: A 2011 perspective, Clin. Res. Hepatol. Gastroenterol., 35, 699, 10.1016/j.clinre.2011.05.016 Cao, 2009, Impact of the underlying mutation and the route of vector administration on immune responses to factor IX in gene therapy for hemophilia B, Cell Ther., 17, 10 Murillo, 2016, Long-term metabolic correction of Wilson’s disease in a murine model by gene therapy, J. Hepatol., 64, 419, 10.1016/j.jhep.2015.09.014 Tavoulari, 2022, Pathogenic variants of the mitochondrial aspartate/glutamate carrier causing citrin deficiency, Trends Endocrinol Metab, 33, 539, 10.1016/j.tem.2022.05.002 Fu, 2011, The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia, J. Gastroenterol., 46, 510, 10.1007/s00535-010-0329-y Yasuda, 2000, Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia, Hum. Genet., 107, 537, 10.1007/s004390000430 Ferla, 2015, Prevalence of anti–adeno-associated virus serotype 8 neutralizing antibodies and arylsulfatase B cross-reactive immunologic material in Mucopolysaccharidosis VI patient candidates for a gene therapy trial, Hum. Gene Ther., 26, 145, 10.1089/hum.2014.109 Mendell, 2010, Dystrophin immunity in Duchenne’s muscular dystrophy, N. Engl. J. Med., 9 Contreras, 2007, Ca2+ activation kinetics of the two aspartate-glutamate mitochondrial carriers, aralar and citrin: role in the heart malate-aspartate NADH shuttle, J. Biol. Chem., 282, 7098, 10.1074/jbc.M610491200 Kramer, 2003, 7, 11 Choi, 1991, A generic intron increases gene expression in transgenic mice, Mol. Cell. Biol., 11, 3070 Clark, 1993, Enhancing the efficiency of transgene expression, Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci., 339, 225, 10.1098/rstb.1993.0020 Duncker, 1997, Introns boost transgene expression in Drosophila melanogaster, Mol. Gen. Genet. MGG, 254, 291, 10.1007/s004380050418 Contreras, 2010, Low levels of citrin ( SLC25A13 ) expression in adult mouse brain restricted to neuronal clusters: citrin expression in the brain, J. Neurosci. Res., 88, 1009, 10.1002/jnr.22283 Goikoetxea-Usandizaga, 2022, Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals, Hepatology., 75, 550, 10.1002/hep.32149 Contreras, 2009, Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways, J. Biol. Chem., 284, 7091, 10.1074/jbc.M808066200 Cuezva, 2002, The bioenergetic signature of cancer: a marker of tumor progression, Cancer Res., 62, 6674 Hung, 2014, Live-cell imaging of cytosolic NADH–NAD+ redox state using a genetically encoded fluorescent biosensor, 83 Hung, 2011, Imaging cytosolic NADH-NAD+ redox state with a genetically encoded fluorescent biosensor, Cell Metab., 14, 545, 10.1016/j.cmet.2011.08.012 Tantama, 2013, Imaging energy status in live cells with a fluorescent biosensor of the intracellular ATP-to-ADP ratio, Nat. Commun., 4, 2550, 10.1038/ncomms3550 Guarás, 2016, The CoQH2/CoQ ratio serves as a sensor of respiratory chain efficiency, Cell Rep., 15, 197, 10.1016/j.celrep.2016.03.009 MacLean, 2010, Skyline: an open source document editor for creating and analyzing targeted proteomics experiments, Bioinformatics., 26, 966, 10.1093/bioinformatics/btq054 Sinasac, 2004, Slc25a13 -knockout mice harbor metabolic deficits but fail to display hallmarks of adult-onset type II Citrullinemia, Mol. Cell. Biol., 24, 527, 10.1128/MCB.24.2.527-536.2004 Koshenov, 2022, Citrin mediated metabolic rewiring in response to altered basal subcellular Ca2+ homeostasis, Commun. Biol., 5, 76, 10.1038/s42003-022-03019-2 Puertas-Frías, 2019, Mitochondrial movement in Aralar/Slc25a12/AGC1 deficient cortical neurons, Neurochem. Int., 131, 10.1016/j.neuint.2019.104541 Dow, 2014, Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice, PLoS One, 9, 10.1371/journal.pone.0095236 Kanzler, 1999, TGF-β1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis, Am. J. Physiol.-Gastrointest. Liver Physiol., 276, G1059, 10.1152/ajpgi.1999.276.4.G1059 Zhang, 2005, Development of an HSV-tk transgenic mouse model for study of liver damage: development of an HSV-tk transgenic mouse model, FEBS J., 272, 2207, 10.1111/j.1742-4658.2005.04644.x Argyros, 2008, Persistent episomal transgene expression in liver following delivery of a scaffold/matrix attachment region containing non-viral vector, Gene Ther., 15, 1593, 10.1038/gt.2008.113 Azimifar, 2014, Cell-type-resolved quantitative proteomics of murine liver, Cell Metab., 20, 1076, 10.1016/j.cmet.2014.11.002 Ölander, 2020, Cell-type-resolved proteomic analysis of the human liver, Liver Int., 40, 1770, 10.1111/liv.14452 Cao, 2019, mRNA therapy improves metabolic and behavioral abnormalities in a murine model of citrin deficiency, Mol. Ther. J. Am. Soc. Gene Ther., 27, 1242, 10.1016/j.ymthe.2019.04.017 Saheki, 2007, Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency, J. Biol. Chem., 282, 25041, 10.1074/jbc.M702031200 Berraondo, 2019, Messenger RNA therapy for rare genetic metabolic diseases, Gut., 68, 1323, 10.1136/gutjnl-2019-318269 Lee, 2018, Urea cycle dysregulation generates clinically relevant genomic and biochemical signatures, Cell., 174, 1559, 10.1016/j.cell.2018.07.019 Rabinovich, 2020, The mitochondrial carrier citrin plays a role in regulating cellular energy during carcinogenesis, Oncogene., 39, 164, 10.1038/s41388-019-0976-2 Hajaj, 2021, The context-specific roles of urea cycle enzymes in tumorigenesis, Mol. Cell, 81, 3749, 10.1016/j.molcel.2021.08.005 Infantino, 2019, Epigenetic upregulation and functional role of the mitochondrial aspartate/glutamate carrier isoform 1 in hepatocellular carcinoma, Biochim. Biophys. Acta (BBA) - Mol. Basis Dis., 1865, 38, 10.1016/j.bbadis.2018.10.018 Medeiros, 2022, The Warburg effect: saturation of mitochondrial NADH shuttles triggers aerobic lactate fermentation, Mol. Cell, 82, 3119, 10.1016/j.molcel.2022.08.004 Wang, 2022, Saturation of the mitochondrial NADH shuttles drives aerobic glycolysis in proliferating cells, Mol. Cell, 82, 3270, 10.1016/j.molcel.2022.07.007 Luengo, 2021, Increased demand for NAD+ relative to ATP drives aerobic glycolysis, Mol. Cell, 81, 691, 10.1016/j.molcel.2020.12.012 Vozza, 2014, UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation, Proc. Natl. Acad. Sci., 111, 960, 10.1073/pnas.1317400111 Raho, 2020, KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth, Nat. Metab., 2, 1373, 10.1038/s42255-020-00315-1 Fiermonte, 2002, Identification of the mitochondrial glutamate transporter, J. Biol. Chem., 277, 19289, 10.1074/jbc.M201572200