IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-018-08187-6.html
   My bibliography  Save this article

Malonylation of GAPDH is an inflammatory signal in macrophages

Author

Listed:
  • Silvia Galván-Peña

    (Trinity College
    GlaxoSmithKline)

  • Richard G. Carroll

    (Royal College of Surgeons in Ireland)

  • Carla Newman

    (GlaxoSmithKline)

  • Elizabeth C. Hinchy

    (University of Cambridge)

  • Eva Palsson-McDermott

    (Trinity College)

  • Elektra K. Robinson

    (UC Santa Cruz)

  • Sergio Covarrubias

    (UC Santa Cruz)

  • Alan Nadin

    (GlaxoSmithKline)

  • Andrew M. James

    (University of Cambridge)

  • Moritz Haneklaus

    (Trinity College)

  • Susan Carpenter

    (UC Santa Cruz)

  • Vincent P. Kelly

    (Trinity College)

  • Michael P. Murphy

    (University of Cambridge)

  • Louise K. Modis

    (GlaxoSmithKline)

  • Luke A. O’Neill

    (Trinity College
    GlaxoSmithKline)

Abstract

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.

Suggested Citation

  • Silvia Galván-Peña & Richard G. Carroll & Carla Newman & Elizabeth C. Hinchy & Eva Palsson-McDermott & Elektra K. Robinson & Sergio Covarrubias & Alan Nadin & Andrew M. James & Moritz Haneklaus & Susa, 2019. "Malonylation of GAPDH is an inflammatory signal in macrophages," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08187-6
    DOI: 10.1038/s41467-018-08187-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-08187-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-08187-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08187-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.