IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-63712-8.html
   My bibliography  Save this article

The shutdown of food digestion due to endoplasmic reticulum homeostasis disruption acts as a protective mechanism in C. elegans

Author

Listed:
  • YongJuan He

    (Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province
    Yunnan University)

  • Yunqing Zhang

    (Yunnan University)

  • Huijuan Xie

    (Yunnan University)

  • Zhao Shan

    (Yunnan University)

  • Zongliu Hou

    (Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province)

  • Bin Qi

    (Yunnan University)

Abstract

Food digestion is essential for nutrient absorption, supporting protein synthesis and maintaining endoplasmic reticulum (ER) homeostasis. However, whether animals can sense ER stress and suppress digestion to reduce ER overload remains unclear. Here, we show that Caenorhabditis elegans can sense ER stress and shut down digestion as a protective response. Food intake activates the unfolded protein response in the ER, and loss of its central regulator, XBP-1, impairs digestion, highlighting the importance of ER homeostasis in food digestion. We identify FDR-1, a food-induced protein, as a key factor that promotes digestion by preserving ER balance through its interaction with DPY-11. Disruption of FDR-1 triggers the innate immune p38/PMK-1 pathway, leading to a protective shutdown of digestion to mitigate ER stress. These findings reveal an adaptive mechanism by which animals limit digestion under ER stress and suggest that modulating nutrient intake may offer therapeutic strategies for diseases related to ER dysfunction.

Suggested Citation

  • YongJuan He & Yunqing Zhang & Huijuan Xie & Zhao Shan & Zongliu Hou & Bin Qi, 2025. "The shutdown of food digestion due to endoplasmic reticulum homeostasis disruption acts as a protective mechanism in C. elegans," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63712-8
    DOI: 10.1038/s41467-025-63712-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-63712-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-63712-8?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. Yating Liu & Qian Li & Guojing Tian & Xinyi Zhou & Panpan Chen & Bo Chen & Zhao Shan & Bin Qi, 2024. "Neuronal PRDX-2-Mediated ROS Signaling Regulates Food Digestion via peripheral UPRmt Activation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Ravi S. Kamath & Andrew G. Fraser & Yan Dong & Gino Poulin & Richard Durbin & Monica Gotta & Alexander Kanapin & Nathalie Le Bot & Sergio Moreno & Marc Sohrmann & David P. Welchman & Peder Zipperlen &, 2003. "Systematic functional analysis of the Caenorhabditis elegans genome using RNAi," Nature, Nature, vol. 421(6920), pages 231-237, January.
    3. Wang Yuan & Yi M. Weaver & Svetlana Earnest & Clinton A. Taylor & Melanie H. Cobb & Benjamin P. Weaver, 2023. "Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Marcella Calfon & Huiqing Zeng & Fumihiko Urano & Jeffery H. Till & Stevan R. Hubbard & Heather P. Harding & Scott G. Clark & David Ron, 2002. "Correction: Corrigendum: IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA," Nature, Nature, vol. 420(6912), pages 202-202, November.
    5. Marcella Calfon & Huiqing Zeng & Fumihiko Urano & Jeffery H. Till & Stevan R. Hubbard & Heather P. Harding & Scott G. Clark & David Ron, 2002. "IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA," Nature, Nature, vol. 415(6867), pages 92-96, January.
    6. Fanrui Hao & Huimin Liu & Bin Qi, 2024. "Bacterial peptidoglycan acts as a digestive signal mediating host adaptation to diverse food resources in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-15, 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. Kimitaka Shibue & Sevim Kahraman & Jorge Ivan Castillo-Quan & Dario F. Jesus & Jiang Hu & Hiroyuki Morita & T. Keith Blackwell & Peng Yi & Rohit N. Kulkarni, 2025. "Genome-wide CRISPR Screen Identifies Sec31A as a Key Regulator of Alpha Cell Survival," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    2. Hanyong Jin & Ji-Hyun Yeom & Eunkyoung Shin & Yoonjie Ha & Haifeng Liu & Daeyoung Kim & Minju Joo & Yong-Hak Kim & Hak Kyun Kim & Minkyung Ryu & Hong-Man Kim & Jeongkyu Kim & Keun P. Kim & Yoonsoo Hah, 2024. "5′-tRNAGly(GCC) halves generated by IRE1α are linked to the ER stress response," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Dadi Jiang & Youming Guo & Tianyu Wang & Liang Wang & Yuelong Yan & Ling Xia & Rakesh Bam & Zhifen Yang & Hyemin Lee & Takao Iwawaki & Boyi Gan & Albert C. Koong, 2024. "IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Fátima Cairrão & Cristiana C. Santos & Adrien Thomas & Scot Marsters & Avi Ashkenazi & Pedro M. Domingos, 2022. "Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Yang Liu & Amrutha K. Avathan Veettil & Raphael Gasper & Mao Jiang & Leon Wagner & Oguz Hastürk & Peng Wu, 2025. "Harnessing indole scaffolds to identify small-molecule IRE1α inhibitors modulating XBP1 mRNA splicing," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    6. Kazuhiro Kashiwagi & Yuichi Shichino & Tatsuya Osaki & Ayako Sakamoto & Madoka Nishimoto & Mari Takahashi & Mari Mito & Friedemann Weber & Yoshiho Ikeuchi & Shintaro Iwasaki & Takuhiro Ito, 2021. "eIF2B-capturing viral protein NSs suppresses the integrated stress response," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    7. Fiamma Salerno & Andrew J. M. Howden & Louise S. Matheson & Özge Gizlenci & Michael Screen & Holger Lingel & Monika C. Brunner-Weinzierl & Martin Turner, 2023. "An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Xiuzhi Li & Xiaolin Wang & Xu Liu & Ge Shan & Liang Chen, 2025. "A UFD1 variant encoding a microprotein modulates UFD1f and IPMK ubiquitination to play pivotal roles in anti-stress responses," Nature Communications, Nature, vol. 16(1), pages 1-24, December.
    9. Ichiro Kawasaki & Kenta Sugiura & Taeko Sasaki & Noriyuki Matsuda & Miyuki Sato & Ken Sato, 2024. "MARC-3, a membrane-associated ubiquitin ligase, is required for fast polyspermy block in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Hope Dang & Raul Castro-Portuguez & Luis Espejo & Grant Backer & Samuel Freitas & Erica Spence & Jeremy Meyers & Karissa Shuck & Emily A. Gardea & Leah M. Chang & Jonah Balsa & Niall Thorns & Caroline, 2023. "On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. Arles Urrutia & Víctor A García-Angulo & Andrés Fuentes & Mauricio Caneo & Marcela Legüe & Sebastián Urquiza & Scarlett E Delgado & Juan Ugalde & Paula Burdisso & Andrea Calixto, 2020. "Bacterially produced metabolites protect C . elegans neurons from degeneration," PLOS Biology, Public Library of Science, vol. 18(3), pages 1-31, March.
    12. Klement Stojanovski & Ioana Gheorghe & Peter Lenart & Anne Lanjuin & William B. Mair & Benjamin D. Towbin, 2023. "Maintenance of appropriate size scaling of the C. elegans pharynx by YAP-1," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Rashmi Tripathi & Nathalie Benz & Bridget Culleton & Pascal Trouvé & Claude Férec, 2014. "Biophysical Characterisation of Calumenin as a Charged F508del-CFTR Folding Modulator," PLOS ONE, Public Library of Science, vol. 9(8), pages 1-15, August.
    14. Malaguti, Giulia & Singh, Param Priya & Isambert, Hervé, 2014. "On the retention of gene duplicates prone to dominant deleterious mutations," Theoretical Population Biology, Elsevier, vol. 93(C), pages 38-51.
    15. Alan Kavšek & Jérôme Salignon & Lluís Millan-Ariño & Patryk Marcinkowski & Ilke Sen & Christian G. Riedel, 2025. "LIN-39 is a neuron-specific developmental determinant of longevity in Caenorhabditis elegans with reduced insulin signaling," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    16. Mustafa C. Camur & Thomas Sharkey & Chrysafis Vogiatzis, 2022. "The Star Degree Centrality Problem: A Decomposition Approach," INFORMS Journal on Computing, INFORMS, vol. 34(1), pages 93-112, January.
    17. Martin Ackermann & Lin Chao, 2006. "DNA Sequences Shaped by Selection for Stability," PLOS Genetics, Public Library of Science, vol. 2(2), pages 1-7, February.
    18. Chrysafis Vogiatzis & Mustafa Can Camur, 2019. "Identification of Essential Proteins Using Induced Stars in Protein–Protein Interaction Networks," INFORMS Journal on Computing, INFORMS, vol. 31(4), pages 703-718, October.
    19. Maria E Gallegos & Sanjeev Balakrishnan & Priya Chandramouli & Shaily Arora & Aruna Azameera & Anitha Babushekar & Emilee Bargoma & Abdulmalik Bokhari & Siva Kumari Chava & Pranti Das & Meetali Desai , 2012. "The C. elegans Rab Family: Identification, Classification and Toolkit Construction," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-19, November.
    20. Jean-Claude Garaud & Jean-Nicolas Schickel & Gilles Blaison & Anne-Marie Knapp & Doulaye Dembele & Julie Ruer-Laventie & Anne-Sophie Korganow & Thierry Martin & Pauline Soulas-Sprauel & Jean-Louis Pas, 2011. "B Cell Signature during Inactive Systemic Lupus Is Heterogeneous: Toward a Biological Dissection of Lupus," PLOS ONE, Public Library of Science, vol. 6(8), pages 1-9, August.

    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_s41467-025-63712-8. 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.