Malonylation of GAPDH is an inflammatory signal in macrophages

被引：195

作者：

Galvan-Pena, Silvia ^{[1
,2
]}

Carroll, Richard G. ^{[3
]}

Newman, Carla ^{[4
]}

Hinchy, Elizabeth C. ^{[5
]}

Palsson-McDermott, Eva ^{[1
]}

Robinson, Elektra K. ^{[6
]}

Covarrubias, Sergio ^{[6
]}

Nadin, Alan ^{[7
]}

James, Andrew M. ^{[5
]}

Haneklaus, Moritz ^{[1
]}

Carpenter, Susan ^{[6
]}

Kelly, Vincent P. ^{[1
]}

Murphy, Michael P. ^{[5
]}

Modis, Louise K. ^{[2
]}

O'Neill, Luke A. ^{[1
,2
]}

机构：

[1] Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin D2, Ireland

[2] GlaxoSmithKline, Immunol Catalyst, Stevenage SG1 2NY, Herts, England

[3] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin D2, Ireland

[4] GlaxoSmithKline, Vitro Vivo Translat, Stevenage SG1 2NY, Herts, England

[5] Univ Cambridge, MRC Mitochondrial Biol Unit, Cambridge CB2 0XY, England

[6] UC Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA

[7] GlaxoSmithKline, NCE Mol Tools Grp, Stevenage SG1 2NY, Herts, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国惠康基金;

关键词：

MITOCHONDRIAL PROTEIN MALONYLATION; FATTY-ACID SYNTHESIS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; LYSINE MALONYLATION; ACETYL-COENZYME; MESSENGER-RNA; INHIBITION; BINDING; SYNTHASE; COMPLEX;

D O I：

10.1038/s41467-018-08187-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 TNF alpha. Upon LPS stimulation, GAPDH undergoes malonylation on lysine 213, leading to its dissociation from TNF alpha mRNA, promoting translation. We therefore identify for the first time malonylation as a signal, regulating GAPDH mRNA binding to promote inflammation.

引用

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