Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1

Evanna L. Mills, Dylan G. Ryan, Hiran A. Prag, Dina Dikovskaya, Deepthi Menon, Zbigniew Zaslona, Mark P. Jedrychowski, Ana S. H. Costa, Maureen Higgins, Emily Hams, John Szpyt, Marah C. Runtsch, Martin S. King, Joanna F. McGouran, Roman Fischer, Benedikt M. Kessler, Anne F. McGettrick, Mark M. Hughes, Richard G. Carroll, Lee M. Booty, Elena V. Knatko, Paul J. Meakin, Michael L. J. Ashford, Louise K. Modis, Gino Brunori, Daniel C. Sévin, Padraic G. Fallon, Stuart T. Caldwell, Edmund R. S. Kunji, Edward T. Chouchani, Christian Frezza, Albena T. Dinkova-Kostova, Richard C. Hartley, Michael P. Murphy and Luke A. O’Neill ()
Additional contact information
Evanna L. Mills: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Dylan G. Ryan: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Hiran A. Prag: MRC Mitochondrial Biology Unit, University of Cambridge,
Dina Dikovskaya: Jacqui Wood Cancer Centre, School of Medicine, University of Dundee
Deepthi Menon: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Zbigniew Zaslona: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Mark P. Jedrychowski: Dana-Farber Cancer Institute, Harvard Medical School
Ana S. H. Costa: MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre
Maureen Higgins: Jacqui Wood Cancer Centre, School of Medicine, University of Dundee
Emily Hams: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin,
John Szpyt: Harvard Medical School
Marah C. Runtsch: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Martin S. King: MRC Mitochondrial Biology Unit, University of Cambridge,
Joanna F. McGouran: School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Roman Fischer: Target Discovery Institute, University of Oxford
Benedikt M. Kessler: Target Discovery Institute, University of Oxford
Anne F. McGettrick: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Mark M. Hughes: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Richard G. Carroll: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Lee M. Booty: GlaxoSmithKline, Gunnelswood Road
Elena V. Knatko: Jacqui Wood Cancer Centre, School of Medicine, University of Dundee
Paul J. Meakin: School of Medicine, University of Dundee
Michael L. J. Ashford: School of Medicine, University of Dundee
Louise K. Modis: GlaxoSmithKline, Gunnelswood Road
Gino Brunori: GlaxoSmithKline
Daniel C. Sévin: Cellzome, GlaxoSmithKline R&D
Padraic G. Fallon: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin,
Stuart T. Caldwell: WestCHEM School of Chemistry, University of Glasgow
Edmund R. S. Kunji: MRC Mitochondrial Biology Unit, University of Cambridge,
Edward T. Chouchani: Dana-Farber Cancer Institute, Harvard Medical School
Christian Frezza: MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre
Albena T. Dinkova-Kostova: Jacqui Wood Cancer Centre, School of Medicine, University of Dundee
Richard C. Hartley: WestCHEM School of Chemistry, University of Glasgow
Michael P. Murphy: MRC Mitochondrial Biology Unit, University of Cambridge,
Luke A. O’Neill: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin,

Nature, 2018, vol. 556, issue 7699, 113-117

Abstract: WebTreatment of lipopolysaccharide-activated macrophages with the cell-permeable itaconate derivative 4-octyl itaconate activates the anti-inflammatory transcription factor Nrf2 by alkylating key cysteine residues on the KEAP1 protein.

Date: 2018
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DOI: 10.1038/nature25986

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