Membrane transporters, the doors of cellular metabolism
Investigation of biochemical features structure/function relationships, metabolic regulation and physio-pathological aspects by in vitro and in vivo experimental models.
Brief description of the research proposal
Transporters are essential cell constituents with a key role in nutrient and metabolite traffic across cell membranes. They control compartmentalized biochemical pathways by allowing metabolite traffic in sub-cellular compartments. Despite a vital role, most transporters are poorly characterized.
We address a specific issue of the transporter knowledge, related to the branched chain amino acids (BCAA) and glutamine (Gln) metabolisms. These are essential or conditionally essential nutrients, involved in energy metabolism, nucleotide and protein synthesis and signaling. BCAA and Gln, once transported inside cells, must enter mitochondria for their metabolic fates. Plasma membrane and mitochondrial transporters for BCAA, Gln and their metabolites are still unknown or partially known.
The project aim consisting in a comprehensive study of transporters involved in BCAA and Gln metabolism, will be achieved by four targets ranging from the biochemical characterization of the transporters and dissection of their physiological role to the expression regulation and the structure/function relationships with important outcomes to human health. Research teams with long standing experience on different types of transporters have been assembled for guaranteeing the project success.
Aims
Establish a deeper understanding of membrane transporters involved in BCAA and Glutamine metabolic pathways to furnish a comprehensive model of amino acid traffic and metabolism
How?
By employing the unique know-how and the complementary competences of the TEAM with a combined approach of in silico, in vitro, ex vivo and in vivo studies
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Year 1
The Link Between the Mitochondrial Fatty Acid Oxidation Derangement and Kidney Injury
Lara Console, Mariafrancesca Scalise, Nicola Giangregorio, Annamaria Tonazzi, Maria Barile and Cesare Indiveri
Drosophila melanogaster Mitochondrial Carriers: Similarities and Differences with the Human Carriers
Rosita Curcio, Paola Lunetti, Vincenzo Zara, Alessandra Ferramosca, Federica Marra, Giuseppe Fiermonte, Anna Rita Cappello, Francesco De Leonardis, Loredana Capobianco and Vincenza Dolce
Tryptophan 224 of the rat mitochondrial carnitine/acylcarnitine carrier is crucial for the antiport mechanism
Nicola Giangregorio, Annamaria Tonazzi, Lara Console, Mariella Pistillo, Vito Scalera, Cesare Indiveri
Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology
Nicola Giangregorio, Annamaria Tonazzi, Lara Console, Mario Prejanò, Tiziana Marino Nino Russo and Cesare Indiveri
Diseases Caused by Mutations in Mitochondrial Carrier Genes SLC25: A Review
Ferdinando Palmieri, Pasquale Scarcia and Magnus Monné
Interaction of Cholesterol With the Human SLC1A5 (ASCT2): Insights Into Structure/Function Relationships
Mariafrancesca Scalise, Lorena Pochini, Jessica Cosco, Emma Aloe, Tiziano Mazza, Lara Console, Antonella Esposito and Cesare Indiveri
Glutamine transporters as pharmacological targets: From function to drug design
Mariafrancesca Scalise, Lorena Pochini, Michele Galluccio, Lara Console, Cesare Indiveri
Chemical Targeting of Membrane Transporters: Insights into Structure/Function Relationships
Mariafrancesca Scalise, Lara Console, Michele Galluccio, Lorena Pochini, and Cesare Indiveri
Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19
Mariafrancesca Scalise and Cesare Indiveri
The Human SLC1A5 Neutral Amino Acid Transporter Catalyzes a pH-Dependent Glutamate/Glutamine Antiport, as Well
Mariafrancesca Scalise, Tiziano Mazza, Gilda Pappacoda, Lorena Pochini, Jessica Cosco, Filomena Rovella1 and Cesare Indiveri
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Year 2
ATP modulates SLC7A5 (LAT1) synergistically with cholesterol
Jessica Cosco, Mariafrancesca Scalise, Claire Colas, Michele Galluccio, Riccardo Martini, Filomena Rovella, Tiziano Mazza, Gerhard F. Ecker and Cesare Indiveri
Mitochondrial Carriers and Substrates Transport Network: A Lesson from Saccharomyces cerevisiae
Alessandra Ferramosca and Vincenzo Zara
The mitochondrial aspartate/glutamate carrier (AGC or Aralar1) isoforms in D. melanogaster: biochemical characterization, gene structure, and evolutionary analysis
Paola Lunetti, Ren´e Massimiliano Marsano, Rosita Curcio, Vincenza Dolce, Giuseppe Fiermonte, Anna Rita Cappello, Federica Marra, Roberta Moschetti, Yuan Li, Donatella Aiello, Araceli del Arco Martínez, Graziantonio Lauria, Francesco De Leonardis, Alessandra Ferramosca, Vincenzo Zara, Loredana Capobianco
Extracellular Citrate Is a Trojan Horse for Cancer Cells
Agata Petillo, Vittorio Abruzzese, Prashant Koshal, Angela Ostuni and Faustino Bisaccia
KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth
Susanna Raho, Loredana Capobianco, Rocco Malivindi, Angelo Vozza, Carmela Piazzolla, Francesco De Leonardis, Ruggiero Gorgoglione, Pasquale Scarcia, Francesca Pezzuto, Gennaro Agrimi, Simona N. Barile, Isabella Pisano, Stephan J. Reshkin, Maria R. Greco, Rosa A. Cardone, Vittoria Rago, Yuan Li, Carlo M. T. Marobbio, Wolfgang Sommergruber, Christopher L. Riley, Francesco M. Lasorsa, Edward Mills, Maria C. Vegliante, Giuseppe E. De Benedetto, Deborah Fratantonio, Luigi Palmieri, Vincenza Dolce and Giuseppe Fiermonte
ASCT1 and ASCT2: Brother and Sister?
Mariafrancesca Scalise, Lara Console, Jessica Cosco, Lorena Pochini, Michele Galluccio, and Cesare Indiveri
Membrane Transporters for Amino Acids as Players of Cancer Metabolic Rewiring
Mariafrancesca Scalise, Lara Console, Filomena Rovella, Michele Galluccio, Lorena Pochini and Cesare Indiveri
Welcome to the Family: Identification of the NAD+ Transporter of Animal Mitochondria as Member of the Solute Carrier Family SLC25
Mathias Ziegler, Magnus Monné, Andrey Nikiforov, Gennaro Agrimi, Ines Heiland and Ferdinando Palmieri
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Year 3
Evidence for Non-Essential Salt Bridges in the M-Gates of Mitochondrial Carrier Proteins
Daniela Valeria Miniero, Magnus Monné, Maria Antonietta Di Noia, Luigi Palmieri, Ferdinando Palmieri
Mitochondrial transport and metabolism of the vitamin Bderived cofactors thiamine pyrophosphate, coenzyme A, FAD and NAD+, and related diseases: A review
Ferdinando Palmieri, Magnus Monné, Giuseppe Fiermonte, Luigi Palmieri
N‑glycosylation is crucial for trafficking and stability of SLC3A2 (CD98)
Lara Console, Mariafrancesca Scalise, Simona Salerno, Raffaella Scanga, Deborah Giudice, Loredana De Bartolo, Annamaria Tonazzi, Cesare Indiveri
Production of recombinant human xCT (SLC7A11) and reconstitution in proteoliposomes for functional studies
Michele Galluccio, Mariafrancesca Scalise, Gilda Pappacoda, Martina Scarpelli, Marcella Bonanomi, Daniela Gaglio, Cesare Indiveri
Strategies for Successful Over-Expression of Human Membrane Transport Systems Using Bacterial Hosts: Future Perspectives
Michele Galluccio, Lara Console, Lorena Pochini, Mariafrancesca Scalise, Nicola Giangregorio, Cesare Indiveri
The involvement of sodium in the function of the human amino acid transporter ASCT2
Tiziano Mazza, Mariafrancesca Scalise, Gilda Pappacoda, Lorena Pochini, Cesare Indiveri
Cysteine 467 of the ASCT2 Amino Acid Transporter Is a Molecular Determinant of the Antiport Mechanism
Mariafrancesca Scalise, Gilda Pappacoda, Tiziano Mazza, Lara Console, Lorena Pochini, Cesare Indiveri
The Nutraceutical Alliin From Garlic Is a Novel Substrate of the Essential Amino Acid Transporter LAT1 (SLC7A5)
Raffaella Scanga, Mariafrancesca Scalise, Filomena Rovella, Teresa Maria Rosaria Regina, Michele Galluccio, Cesare Indiveri
Multiple roles played by the mitochondrial citrate carrier in cellular metabolism and physiology
Vincenzo Zara, Graziana Assalve, Alessandra Ferramosca
Two functionally different mitochondrial phosphate carriers support Drosophila melanogaster OXPHOS throughout distinct developmental stages
Rosita Curcio, Luca Frattaruolo, Federica Marra, Graziano Pesole, Angelo Vozza, Anna Rita Cappello, Marco Fiorillo, Graziantonio Lauria, Amer Ahmed, Giuseppe Fiermonte, Loredana Capobianco, Vincenza Dolce
Inactivation of HAP4 Accelerates RTG-Dependent Osmoadaptation in Saccharomyces cerevisiae
Maria Antonietta Di Noia, Pasquale Scarcia, Gennaro Agrimi, Ohiemi Benjamin Ocheja, Ehtisham Wahid, Isabella Pisano, Eleonora Paradies, Luigi Palmieri, Cataldo Guaragnella, Nicoletta Guaragnella
A Picrocrocin-Enriched Fraction from a Saffron Extract Affects Lipid Homeostasis in HepG2 Cells through a Non-Statin-like Mode
Luca Frattaruolo, Federica Marra, Graziantonio Lauria, Carlo Siciliano, Rosita Curcio, Luigina Muto, Matteo Brindisi, Donatella Aiello, Anna Napoli, Giuseppe Fiermonte, Anna Rita Cappello, Marco Fiorillo, Amer Ahmed,Vincenza Dolce
Over-Production of the Human SLC7A10 in E. coli and Functional Assay in Proteoliposomes
Michele Galluccio, Tiziano Mazza, Mariafrancesca Scalise, Martina Tripicchio, Martina Scarpelli, Maria Tolomeo, Lorena Pochini, Cesare Indiveri
Glutamine-Derived Aspartate Biosynthesis in Cancer Cells: Role of Mitochondrial Transporters and New Therapeutic Perspectives
Ruggiero Gorgoglione, Valeria Impedovo, Christopher L. Riley, Deborah Fratantonio, Stefano Tiziani, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte
Generation of a Yeast Cell Model Potentially Useful to Identify the Mammalian Mitochondrial N-Acetylglutamate Transporter
Ruggiero Gorgoglione, Roberta Seccia, Amer Ahmed, Angelo Vozza, Loredana Capobianco, Alessia Lodi, Federica Marra, Eleonora Paradies, Luigi Palmieri, Vincenzo Coppola, Vincenza Dolce, Giuseppe Fiermonte
Praseodymium trivalent ion is an effective inhibitor of mitochondrial basic amino acids and carnitine/acylcarnitine carriers
Giovanna Incampo, Nicola Giangregorio, Nicola Gambacorta, Orazio Nicolotti, Concetta Pacifico, Luigi Palmieri, Annamaria Tonazzi
Role of Mitochondrial Transporters on Metabolic Rewiring of Pancreatic Adenocarcinoma: A Comprehensive Review
Graziantonio Lauria, Rosita Curcio, Paola Lunetti, Stefano Tiziani, Vincenzo Coppola, Vincenza Dolce, Giuseppe Fiermonte, and Amer Ahmed
Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate
Paola Lunetti, Ruggiero Gorgoglione, Rosita Curcio, Federica Marra, Antonella Pignataro, Angelo Vozza, Christopher L. Riley, Loredana Capobianco, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte
An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases
Federica Marra, Paola Lunetti, Rosita Curcio, Francesco Massimo Lasorsa, Loredana Capobianco, Vito Porcelli, Vincenza Dolce, Giuseppe Fiermonte, Pasquale Scarcia
Evidence for Non-Essential Salt Bridges in the M-Gates of Mitochondrial Carrier Proteins
Daniela Valeria Miniero, Magnus Monné, Maria Antonietta Di Noia, Luigi Palmieri, Ferdinando Palmieri
Mitochondrial transport and metabolism of the major methyl donor and versatile cofactor S-adenosylmethionine, and related diseases: A review
Magnus Monné, Carlo M. T. Marobbio, Gennaro Agrimi, Luigi Palmieri, Ferdinando Palmieri
New Insights into the Evolution and Gene Structure of the Mitochondrial Carrier Family Unveiled by Analyzing the Frequent and Conserved Intron Positions
Magnus Monné, Antonia Cianciulli, Maria A. Panaro, Rosa Calvello, Anna De Grassi, Luigi Palmieri, Vincenzo Mitolo, Ferdinando Palmieri
The Regulation of Fat Metabolism during Aerobic Exercise
Antonella Muscella, Erika Stefàno, Paola Lunetti, Loredana Capobianco, Santo Marsigliante
Citrate Regulates the Saccharomyces cerevisiae Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP
Roberta Seccia, Silvia De Santis, Maria A. Di Noia, Ferdinando Palmieri, Daniela V. Miniero, Raffaele Marmo, Eleonora Paradies, Antonella Santoro, Ciro L. Pierri, Luigi Palmieri, Carlo M. T. Marobbio, Angelo Vozza
Multiple roles played by the mitochondrial citrate carrier in cellular metabolism and physiology
Vincenzo Zara, Graziana Assalve, Alessandra Ferramosca
