IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49543-z.html
   My bibliography  Save this article

A tripartite organelle platform links growth factor receptor signaling to mitochondrial metabolism

Author

Listed:
  • Deborah Mesa

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

  • Elisa Barbieri

    (European Institute of Oncology IRCCS)

  • Andrea Raimondi

    (IRCCS San Raffaele Hospital Scientific Institute
    Institute for Research in Biomedicine)

  • Stefano Freddi

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

  • Giorgia Miloro

    (European Institute of Oncology IRCCS)

  • Gorana Jendrisek

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

  • Giusi Caldieri

    (European Institute of Oncology IRCCS)

  • Micaela Quarto

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

  • Irene Schiano Lomoriello

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

  • Maria Grazia Malabarba

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

  • Arianna Bresci

    (Politecnico di Milano)

  • Francesco Manetti

    (Politecnico di Milano)

  • Federico Vernuccio

    (Politecnico di Milano)

  • Hind Abdo

    (The AIRC Institute of Molecular Oncology)

  • Giorgio Scita

    (Università degli Studi di Milano
    The AIRC Institute of Molecular Oncology)

  • Letizia Lanzetti

    (University of Torino Medical School
    FPO-IRCCS)

  • Dario Polli

    (Politecnico di Milano
    CNR Institute for Photonics and Nanotechnology (CNR-IFN))

  • Carlo Tacchetti

    (IRCCS San Raffaele Hospital Scientific Institute
    Vita-Salute San Raffaele University)

  • Paolo Pinton

    (University of Ferrara)

  • Massimo Bonora

    (University of Ferrara)

  • Pier Paolo Di Fiore

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

  • Sara Sigismund

    (Università degli Studi di Milano
    European Institute of Oncology IRCCS)

Abstract

One open question in the biology of growth factor receptors is how a quantitative input (i.e., ligand concentration) is decoded by the cell to produce specific response(s). Here, we show that an EGFR endocytic mechanism, non-clathrin endocytosis (NCE), which is activated only at high ligand concentrations and targets receptor to degradation, requires a tripartite organelle platform involving the plasma membrane (PM), endoplasmic reticulum (ER) and mitochondria. At these contact sites, EGFR-dependent, ER-generated Ca2+ oscillations are sensed by mitochondria, leading to increased metabolism and ATP production. Locally released ATP is required for cortical actin remodeling and EGFR-NCE vesicle fission. The same biochemical circuitry is also needed for an effector function of EGFR, i.e., collective motility. The multiorganelle signaling platform herein described mediates direct communication between EGFR signaling and mitochondrial metabolism, and is predicted to have a broad impact on cell physiology as it is activated by another growth factor receptor, HGFR/MET.

Suggested Citation

  • Deborah Mesa & Elisa Barbieri & Andrea Raimondi & Stefano Freddi & Giorgia Miloro & Gorana Jendrisek & Giusi Caldieri & Micaela Quarto & Irene Schiano Lomoriello & Maria Grazia Malabarba & Arianna Bre, 2024. "A tripartite organelle platform links growth factor receptor signaling to mitochondrial metabolism," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49543-z
    DOI: 10.1038/s41467-024-49543-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49543-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49543-z?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. Joshua M. Baughman & Fabiana Perocchi & Hany S. Girgis & Molly Plovanich & Casey A. Belcher-Timme & Yasemin Sancak & X. Robert Bao & Laura Strittmatter & Olga Goldberger & Roman L. Bogorad & Victor Ko, 2011. "Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter," Nature, Nature, vol. 476(7360), pages 341-345, August.
    2. Luca Scorrano & Maria Antonietta Matteis & Scott Emr & Francesca Giordano & György Hajnóczky & Benoît Kornmann & Laura L. Lackner & Tim P. Levine & Luca Pellegrini & Karin Reinisch & Rosario Rizzuto &, 2019. "Coming together to define membrane contact sites," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    3. Annalisa Petrelli & Giorgio F. Gilestro & Stefania Lanzardo & Paolo M. Comoglio & Nicola Migone & Silvia Giordano, 2002. "The endophilin–CIN85–Cbl complex mediates ligand-dependent downregulation of c-Met," Nature, Nature, vol. 416(6877), pages 187-190, March.
    4. Diego De Stefani & Anna Raffaello & Enrico Teardo & Ildikò Szabò & Rosario Rizzuto, 2011. "A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter," Nature, Nature, vol. 476(7360), pages 336-340, August.
    5. Henri-François Renard & Mijo Simunovic & Joël Lemière & Emmanuel Boucrot & Maria Daniela Garcia-Castillo & Senthil Arumugam & Valérie Chambon & Christophe Lamaze & Christian Wunder & Anne K. Kenworthy, 2015. "Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis," Nature, Nature, vol. 517(7535), pages 493-496, January.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Paloma García Casas & Michela Rossini & Linnea Påvénius & Mezida Saeed & Nikita Arnst & Sonia Sonda & Tânia Fernandes & Irene D’Arsiè & Matteo Bruzzone & Valeria Berno & Andrea Raimondi & Maria Livia , 2024. "Simultaneous detection of membrane contact dynamics and associated Ca2+ signals by reversible chemogenetic reporters," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

    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. Caterina Marchioretti & Giulia Zanetti & Marco Pirazzini & Gaia Gherardi & Leonardo Nogara & Roberta Andreotti & Paolo Martini & Lorenzo Marcucci & Marta Canato & Samir R. Nath & Emanuela Zuccaro & Ma, 2023. "Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca2+ accumulation in spinobulbar muscular atrophy skeletal muscle," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Mariana P. Cervantes-Silva & Richard G. Carroll & Mieszko M. Wilk & Diana Moreira & Cloe A. Payet & James R. O’Siorain & Shannon L. Cox & Lauren E. Fagan & Paula A. Klavina & Yan He & Tabea Drewinski , 2022. "The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Mohammad Naimul Islam & Galina A. Gusarova & Shonit R. Das & Li Li & Eiji Monma & Murari Anjaneyulu & Liberty Mthunzi & Sadiqa K. Quadri & Edward Owusu-Ansah & Sunita Bhattacharya & Jahar Bhattacharya, 2022. "The mitochondrial calcium uniporter of pulmonary type 2 cells determines severity of acute lung injury," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Enrique Balderas & David R. Eberhardt & Sandra Lee & John M. Pleinis & Salah Sommakia & Anthony M. Balynas & Xue Yin & Mitchell C. Parker & Colin T. Maguire & Scott Cho & Marta W. Szulik & Anna Bakhti, 2022. "Mitochondrial calcium uniporter stabilization preserves energetic homeostasis during Complex I impairment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Raluca Groza & Kita Valerie Schmidt & Paul Markus Müller & Paolo Ronchi & Claire Schlack-Leigers & Ursula Neu & Dmytro Puchkov & Rumiana Dimova & Claudia Matthaeus & Justin Taraska & Thomas R. Weikl &, 2024. "Adhesion energy controls lipid binding-mediated endocytosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Eunbyul Cho & Youngsik Woo & Yeongjun Suh & Bo Kyoung Suh & Soo Jeong Kim & Truong Thi My Nhung & Jin Yeong Yoo & Tran Diem Nghi & Su Been Lee & Dong Jin Mun & Sang Ki Park, 2023. "Ratiometric measurement of MAM Ca2+ dynamics using a modified CalfluxVTN," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Patrick A. Sandoz & Robin A. Denhardt-Eriksson & Laurence Abrami & Luciano A. Abriata & Gard Spreemann & Catherine Maclachlan & Sylvia Ho & Béatrice Kunz & Kathryn Hess & Graham Knott & Francisco S. M, 2023. "Dynamics of CLIMP-63 S-acylation control ER morphology," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Olga A. Balashova & Alexios A. Panoutsopoulos & Olesya Visina & Jacob Selhub & Paul S. Knoepfler & Laura N. Borodinsky, 2024. "Noncanonical function of folate through folate receptor 1 during neural tube formation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Anabel-Lise Le Roux & Caterina Tozzi & Nikhil Walani & Xarxa Quiroga & Dobryna Zalvidea & Xavier Trepat & Margarita Staykova & Marino Arroyo & Pere Roca-Cusachs, 2021. "Dynamic mechanochemical feedback between curved membranes and BAR protein self-organization," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    10. Hans J C T Wessels & Rutger O Vogel & Robert N Lightowlers & Johannes N Spelbrink & Richard J Rodenburg & Lambert P van den Heuvel & Alain J van Gool & Jolein Gloerich & Jan A M Smeitink & Leo G Nijtm, 2013. "Analysis of 953 Human Proteins from a Mitochondrial HEK293 Fraction by Complexome Profiling," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-14, July.
    11. Samsuzzoha Mondal & Karthik Narayan & Samuel Botterbusch & Imania Powers & Jason Zheng & Honey Priya James & Rui Jin & Tobias Baumgart, 2022. "Multivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    12. Doron Stupp & Elad Sharon & Idit Bloch & Marinka Zitnik & Or Zuk & Yuval Tabach, 2021. "Co-evolution based machine-learning for predicting functional interactions between human genes," Nature Communications, Nature, vol. 12(1), pages 1-14, 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_s41467-024-49543-z. 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.