IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-62895-4.html
   My bibliography  Save this article

Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria

Author

Listed:
  • Tetiana Serdiuk

    (ETH Zürich)

  • Yanick Fleischmann

    (ETH Zürich)

  • Dhiman Ghosh

    (ETH Zürich)

  • Aro Delparente

    (ETH Zürich)

  • Viviane Reber

    (ETH Zürich)

  • Larissa Frey

    (ETH Zürich)

  • David Rhyner

    (ETH Zürich)

  • Juan Gerez

    (ETH Zürich)

  • Norbert Volkmar

    (ETH Zürich)

  • Lucie Kralickova

    (ETH Zürich)

  • Guillaume Mas

    (University of Basel)

  • Christian Dörig

    (ETH Zürich)

  • Sebastian Hiller

    (University of Basel)

  • Roger Schibli

    (ETH Zürich)

  • Linjing Mu

    (ETH Zürich)

  • Paola Picotti

    (ETH Zürich)

  • Roland Riek

    (ETH Zürich)

Abstract

Mitochondrial dysfunction and accumulation of α-synuclein aggregates are hallmarks of the neurodegenerative Parkinson’s disease and may be interconnected. To investigate the interplay between α-synuclein and brain mitochondria at near atomic structural level, we apply NMR and identify α-synuclein protein interactors using limited proteolysis-coupled mass spectrometry (LiP-MS). Several of the proteins identified are related to ATP synthesis and homeostasis and include subunits of ATP synthase and the adenylate kinase AK2. Furthermore, our data suggest that α-synuclein interacts with the Parkinson’s disease-related protein DJ1. NMR analysis demonstrates that both AK2 and DJ1 bind to the C-terminus and other segments of α-synuclein. Using a functional assay for AK2, we show that monomeric α-synuclein has an activating effect, whereas C-terminally truncated α-synuclein and α-synuclein in an amyloid fibrillar state have no significant effect on AK2 activity. Our results suggest that α-synuclein modulates ATP homeostasis in a manner dependent on its conformation and its C-terminal acidic segment.

Suggested Citation

  • Tetiana Serdiuk & Yanick Fleischmann & Dhiman Ghosh & Aro Delparente & Viviane Reber & Larissa Frey & David Rhyner & Juan Gerez & Norbert Volkmar & Lucie Kralickova & Guillaume Mas & Christian Dörig &, 2025. "Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62895-4
    DOI: 10.1038/s41467-025-62895-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-62895-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-62895-4?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:16:y:2025:i:1:d:10.1038_s41467-025-62895-4. 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.