title: Intermediates of Metabolism: From Bystanders to Signalling Molecules.
abstract: The integration of biochemistry into immune cell biology has contributed immensely to our understanding of immune cell function and the associated pathologies. So far, most studies have focused on the regulation of metabolic pathways during an immune response and their contribution to its success. More recently, novel signalling functions of metabolic intermediates are being discovered that might play important roles in the regulation of immunity. Here we describe the three long-known small metabolites lactate, acetyl-CoA, and succinate in the context of immunometabolic signalling. Functions of these ubiquitous molecules are largely dependent on their intra- and extracellular concentrations as well as their subcompartmental localisation. Importantly, the signalling functions of these metabolic intermediates extend beyond self-regulatory roles and include cell-to-cell communication and sensing of microenvironmental conditions to elicit stress responses and cellular adaptation.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Haas
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK; Istituto Pasteur, Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Cucchi
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Smith
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK; Department of Translational Medical Sciences, University of Naples 'Federico II', Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pucino
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Claire Elizabeth
authors.initials: CE
authors.lastname: Macdougall
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK. Electronic address: c.mauro@qmul.ac.uk.
authors.forename: Claudio
authors.initials: C
authors.lastname: Mauro
mesh_terms: D000105:Acetyl Coenzyme A / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002952:Citric Acid Cycle / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005227:Fatty Acids / Q000276:immunology / Q000378:metabolism; D006019:Glycolysis / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D019344:Lactic Acid / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D019802:Succinic Acid / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D005227:Fatty Acids; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; D019802:Succinic Acid
keywords: fatty acid oxidation; glycolysis; lactate; succinate; tricarboxylic acid cycle