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Down-regulation of the mitochondrial aspartate-glutamate carrier isoform 1 AGC1 inhibits proliferation and N-acetylaspartate synthesis in Neuro2A cells.
Profilo, Emanuela; Peña-Altamira, Luis Emiliano; Corricelli, Mariangela; Castegna, Alessandra; Danese, Alberto; Agrimi, Gennaro; Petralla, Sabrina; Giannuzzi, Giulia; Porcelli, Vito; Sbano, Luigi; Viscomi, Carlo; Massenzio, Francesca; Palmieri, Erika Mariana; Giorgi, Carlotta; Fiermonte, Giuseppe; Virgili, Marco; Palmieri, Luigi; Zeviani, Massimo; Pinton, Paolo; Monti, Barbara; Palmieri, Ferdinando; Lasorsa, Francesco Massimo.
Afiliación
  • Profilo E; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy.
  • Peña-Altamira LE; Department of Pharmacy and BioTechnology, University of Bologna, Bologna 40126, Italy.
  • Corricelli M; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara 44121, Italy.
  • Castegna A; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy.
  • Danese A; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara 44121, Italy.
  • Agrimi G; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy.
  • Petralla S; Department of Pharmacy and BioTechnology, University of Bologna, Bologna 40126, Italy.
  • Giannuzzi G; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy.
  • Porcelli V; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy.
  • Sbano L; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara 44121, Italy.
  • Viscomi C; MRC-Mitochondrial Biology Unit, Cambridge, UK; Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
  • Massenzio F; Department of Pharmacy and BioTechnology, University of Bologna, Bologna 40126, Italy.
  • Palmieri EM; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy.
  • Giorgi C; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara 44121, Italy.
  • Fiermonte G; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy.
  • Virgili M; Department of Pharmacy and BioTechnology, University of Bologna, Bologna 40126, Italy.
  • Palmieri L; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy; Institute of Biomembranes and Bioenergetics, Consiglio Nazionale delle Ricerche, Bari 70126, Italy.
  • Zeviani M; MRC-Mitochondrial Biology Unit, Cambridge, UK; Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
  • Pinton P; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara 44121, Italy.
  • Monti B; Department of Pharmacy and BioTechnology, University of Bologna, Bologna 40126, Italy.
  • Palmieri F; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Bari 70125, Italy; Institute of Biomembranes and Bioenergetics, Consiglio Nazionale delle Ricerche, Bari 70126, Italy. Electronic address: ferdinando.palmieri@uniba.it.
  • Lasorsa FM; Institute of Biomembranes and Bioenergetics, Consiglio Nazionale delle Ricerche, Bari 70126, Italy. Electronic address: fm.lasorsa@ibbe.cnr.it.
Biochim Biophys Acta Mol Basis Dis ; 1863(6): 1422-1435, 2017 06.
Article en En | MEDLINE | ID: mdl-28235644
The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) catalyzes a Ca2+-stimulated export of aspartate to the cytosol in exchange for glutamate, and is a key component of the malate-aspartate shuttle which transfers NADH reducing equivalents from the cytosol to mitochondria. By sustaining the complete glucose oxidation, AGC1 is thought to be important in providing energy for cells, in particular in the CNS and muscle where this protein is mainly expressed. Defects in the AGC1 gene cause AGC1 deficiency, an infantile encephalopathy with delayed myelination and reduced brain N-acetylaspartate (NAA) levels, the precursor of myelin synthesis in the CNS. Here, we show that undifferentiated Neuro2A cells with down-regulated AGC1 display a significant proliferation deficit associated with reduced mitochondrial respiration, and are unable to synthesize NAA properly. In the presence of high glutamine oxidation, cells with reduced AGC1 restore cell proliferation, although oxidative stress increases and NAA synthesis deficit persists. Our data suggest that the cellular energetic deficit due to AGC1 impairment is associated with inappropriate aspartate levels to support neuronal proliferation when glutamine is not used as metabolic substrate, and we propose that delayed myelination in AGC1 deficiency patients could be attributable, at least in part, to neuronal loss combined with lack of NAA synthesis occurring during the nervous system development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación hacia Abajo / Ácido Aspártico / Sistemas de Transporte de Aminoácidos / Proteínas Mitocondriales / Proliferación Celular / Neuronas Límite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2017 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación hacia Abajo / Ácido Aspártico / Sistemas de Transporte de Aminoácidos / Proteínas Mitocondriales / Proliferación Celular / Neuronas Límite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2017 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos