Malonylation of GAPDH is an inflammatory signal in macrophages.
2019
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
glycolysisand altering the
Krebs cycle. Here we describe a role for the citrate-derived metabolite
malonyl-CoAin 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.
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