IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49646-7.html
   My bibliography  Save this article

Non-consecutive enzyme interactions within TCA cycle supramolecular assembly regulate carbon-nitrogen metabolism

Author

Listed:
  • Weronika Jasinska

    (Ben-Gurion University of the Negev)

  • Mirco Dindo

    (Okinawa Institute of Science and Technology Graduate University
    University of Perugia)

  • Sandra M. C. Cordoba

    (Max-Planck-Institut fur Molekulare Pflanzenphysiologie)

  • Adrian W. R. Serohijos

    (Universite de Montreal
    Universite de Montreal)

  • Paola Laurino

    (Okinawa Institute of Science and Technology Graduate University
    Osaka University)

  • Yariv Brotman

    (Ben-Gurion University of the Negev)

  • Shimon Bershtein

    (Ben-Gurion University of the Negev)

Abstract

Enzymes of the central metabolism tend to assemble into transient supramolecular complexes. However, the functional significance of the interactions, particularly between enzymes catalyzing non-consecutive reactions, remains unclear. Here, by co-localizing two non-consecutive enzymes of the TCA cycle from Bacillus subtilis, malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICD), in phase separated droplets we show that MDH-ICD interaction leads to enzyme agglomeration with a concomitant enhancement of ICD catalytic rate and an apparent sequestration of its reaction product, 2-oxoglutarate. Theory demonstrates that MDH-mediated clustering of ICD molecules explains the observed phenomena. In vivo analyses reveal that MDH overexpression leads to accumulation of 2-oxoglutarate and reduction of fluxes flowing through both the catabolic and anabolic branches of the carbon-nitrogen intersection occupied by 2-oxoglutarate, resulting in impeded ammonium assimilation and reduced biomass production. Our findings suggest that the MDH-ICD interaction is an important coordinator of carbon-nitrogen metabolism.

Suggested Citation

  • Weronika Jasinska & Mirco Dindo & Sandra M. C. Cordoba & Adrian W. R. Serohijos & Paola Laurino & Yariv Brotman & Shimon Bershtein, 2024. "Non-consecutive enzyme interactions within TCA cycle supramolecular assembly regulate carbon-nitrogen metabolism," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49646-7
    DOI: 10.1038/s41467-024-49646-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49646-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49646-7?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
    ---><---

    References listed on IDEAS

    as
    1. Youjun Zhang & Katherine F. M. Beard & Corné Swart & Susan Bergmann & Ina Krahnert & Zoran Nikoloski & Alexander Graf & R. George Ratcliffe & Lee J. Sweetlove & Alisdair R. Fernie & Toshihiro Obata, 2017. "Protein-protein interactions and metabolite channelling in the plant tricarboxylic acid cycle," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    2. Lee J. Sweetlove & Alisdair R. Fernie, 2018. "The role of dynamic enzyme assemblies and substrate channelling in metabolic regulation," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Alastair G. Kerr & Zuoneng Wang & Na Wang & Kelvin H. M. Kwok & Jutta Jalkanen & Alison Ludzki & Simon Lecoutre & Dominique Langin & Martin O. Bergo & Ingrid Dahlman & Carsten Mim & Peter Arner & Hui , 2022. "The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Joyce C. Breger & James N. Vranish & Eunkeu Oh & Michael H. Stewart & Kimihiro Susumu & Guillermo Lasarte-Aragonés & Gregory A. Ellis & Scott A. Walper & Sebastián A. Díaz & Shelby L. Hooe & William , 2023. "Self assembling nanoparticle enzyme clusters provide access to substrate channeling in multienzymatic cascades," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. György Abrusán & Aleksej Zelezniak, 2024. "Cellular location shapes quaternary structure of enzymes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Liangxiao Tan & Jun-Hao Zhou & Jian-Ke Sun & Jiayin Yuan, 2022. "Electrostatically cooperative host-in-host of metal cluster ⊂ ionic organic cages in nanopores for enhanced catalysis," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    5. Xixi Sun & Yujie Yuan & Qitong Chen & Shiqi Nie & Jiaxuan Guo & Zutian Ou & Min Huang & Zixin Deng & Tiangang Liu & Tian Ma, 2022. "Metabolic pathway assembly using docking domains from type I cis-AT polyketide synthases," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    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:15:y:2024:i:1:d:10.1038_s41467-024-49646-7. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.