IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23047-6.html
   My bibliography  Save this article

Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of β-catenin signaling

Author

Listed:
  • Young-Mee Kim

    (University of Illinois at Chicago
    University of Illinois at Chicago
    University of Illinois Cancer Center, University of Illinois at Chicago)

  • Sarah Krantz

    (University of Illinois at Chicago
    University of Illinois at Chicago)

  • Ankit Jambusaria

    (University of Illinois at Chicago
    University of Illinois at Chicago
    University of Illinois at Chicago)

  • Peter T. Toth

    (University of Illinois at Chicago
    University of Illinois at Chicago)

  • Hyung-Geun Moon

    (Department of Medicine, University of Illinois at Chicago)

  • Isuru Gunarathna

    (University of Illinois at Chicago
    University of Illinois at Chicago)

  • Gye Young Park

    (Department of Medicine, University of Illinois at Chicago)

  • Jalees Rehman

    (University of Illinois at Chicago
    University of Illinois at Chicago
    University of Illinois Cancer Center, University of Illinois at Chicago
    University of Illinois at Chicago)

Abstract

Endothelial barrier integrity is ensured by the stability of the adherens junction (AJ) complexes comprised of vascular endothelial (VE)-cadherin as well as accessory proteins such as β-catenin and p120-catenin. Disruption of the endothelial barrier due to disassembly of AJs results in tissue edema and the influx of inflammatory cells. Using three-dimensional structured illumination microscopy, we observe that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane with VE-cadherin and β-catenin in endothelial cells during homeostasis. Upon inflammatory stimulation, Mfn2 is sulfenylated, the Mfn2/β-catenin complex disassociates from the AJs and Mfn2 accumulates in the nucleus where Mfn2 negatively regulates the transcriptional activity of β-catenin. Endothelial-specific deletion of Mfn2 results in inflammatory activation, indicating an anti-inflammatory role of Mfn2 in vivo. Our results suggest that Mfn2 acts in a non-canonical manner to suppress the inflammatory response by stabilizing cell–cell adherens junctions and by binding to the transcriptional activator β-catenin.

Suggested Citation

  • Young-Mee Kim & Sarah Krantz & Ankit Jambusaria & Peter T. Toth & Hyung-Geun Moon & Isuru Gunarathna & Gye Young Park & Jalees Rehman, 2021. "Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of β-catenin signaling," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23047-6
    DOI: 10.1038/s41467-021-23047-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23047-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23047-6?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:12:y:2021:i:1:d:10.1038_s41467-021-23047-6. 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.