Reference : Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Life sciences : Microbiology
http://hdl.handle.net/10993/2256
Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
English
Michelucci, Alessandro mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Cordes, Thekla mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Ghelfi, Jenny mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Pailot, Arnaud mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Reiling, Norbert [> >]
Goldmann, Oliver [> >]
Binz, Tina [> >]
Wegner, André mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Tallam, Aravind mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Rausell, Antonio [> >]
Buttini, Manuel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Linster, Carole mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Medina, Eva [> >]
Balling, Rudi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Hiller, Karsten mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
22-Apr-2013
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
Yes (verified by ORBilu)
International
0027-8424
1091-6490
Washington
DC
[en] Immunoresponsive gene 1 (Irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis-aconitate, a tricarboxylic acid cycle intermediate. Using a gain-and-loss-of-function approach in both mouse and human immune cells, we found Irg1 expression levels correlating with the amounts of itaconic acid, a metabolite previously proposed to have an antimicrobial effect. We purified IRG1 protein and identified its cis-aconitate decarboxylating activity in an enzymatic assay. Itaconic acid is an organic compound that inhibits isocitrate lyase, the key enzyme of the glyoxylate shunt, a pathway essential for bacterial growth under specific conditions. Here we show that itaconic acid inhibits the growth of bacteria expressing isocitrate lyase, such as Salmonella enterica and Mycobacterium tuberculosis. Furthermore, Irg1 gene silencing in macrophages resulted in significantly decreased intracellular itaconic acid levels as well as significantly reduced antimicrobial activity during bacterial infections. Taken together, our results demonstrate that IRG1 links cellular metabolism with immune defense by catalyzing itaconic acid production.
Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Enzymology & Metabolism (Linster Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Computational Biology (Del Sol Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Metabolomics (Hiller Group)
Researchers ; Professionals ; Students ; General public ; Others
http://hdl.handle.net/10993/2256
10.1073/pnas.1218599110
http://www.pnas.org/content/early/2013/04/18/1218599110

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