Malonylation of GAPDH is an inflammatory signal in macrophages.

TitleMalonylation of GAPDH is an inflammatory signal in macrophages.
Publication TypeJournal Article
Year of Publication2019
AuthorsGalván-Peña, S, Carroll, RG, Newman, C, Hinchy, EC, Palsson-McDermott, E, Robinson, EK, Covarrubias, S, Nadin, A, James, AM, Haneklaus, M, Carpenter, S, Kelly, VP, Murphy, MP, Modis, LK, O'Neill, LA
JournalNat Commun
Date Published2019 01 18
KeywordsAnimals, Cytokines, Glyceraldehyde-3-Phosphate Dehydrogenases, HEK293 Cells, Humans, Inflammation, Inflammation Mediators, Lipopolysaccharides, Lysine, Macrophages, Malonyl Coenzyme A, Mice, Inbred C57BL, Mutagenesis, Polyribosomes, RNA, Messenger, RNA, Small Interfering, RNA-Binding Proteins, Tumor Necrosis Factor-alpha

Macrophages undergo metabolic changes during activation that are coupled to functional responses. The gram negative bacterial product lipopolysaccharide (LPS) is especially potent at driving metabolic reprogramming, enhancing glycolysis and altering the Krebs cycle. Here we describe a role for the citrate-derived metabolite malonyl-CoA in the effect of LPS in macrophages. Malonylation of a wide variety of proteins occurs in response to LPS. We focused on one of these, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In resting macrophages, GAPDH binds to and suppresses translation of several inflammatory mRNAs, including that encoding TNFα. Upon LPS stimulation, GAPDH undergoes malonylation on lysine 213, leading to its dissociation from TNFα mRNA, promoting translation. We therefore identify for the first time malonylation as a signal, regulating GAPDH mRNA binding to promote inflammation.

Alternate JournalNat Commun
Citation Key10.1038/s41467-018-08187-6
PubMed ID30659183
PubMed Central IDPMC6338787
Grant List / / Wellcome Trust / United Kingdom