title: Succinate: a metabolic signal in inflammation.
abstract: Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria. Recently, new roles for succinate outside metabolism have emerged. Succinate stabilizes the transcription factor hypoxia-inducible factor-1α (HIF-1α) in specific tumors and in activated macrophages, and stimulates dendritic cells via its receptor succinate receptor 1. Furthermore, succinate has been shown to post-translationally modify proteins. This expanding repertoire of functions for succinate suggests a broader role in cellular activation. We review the new roles of succinate and draw parallels to other metabolites such as NAD(+) and citrate whose roles have expanded beyond metabolism and into signaling.
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Evanna
authors.initials: E
authors.lastname: Mills
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. Electronic address: laoneill@tcd.ie.
authors.forename: Luke A J
authors.initials: LA
authors.lastname: O'Neill
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002952:Citric Acid Cycle; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D043562:Receptors, G-Protein-Coupled; D019802:Succinic Acid
keywords: HIF-1α; SUCNR1; inflammation; metabolism; succinate; succinylation