IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28930-4.html
   My bibliography  Save this article

iRhom pseudoproteases regulate ER stress-induced cell death through IP3 receptors and BCL-2

Author

Listed:
  • Iqbal Dulloo

    (University of Oxford)

  • Peace Atakpa-Adaji

    (University of Cambridge)

  • Yi-Chun Yeh

    (University of Oxford)

  • Clémence Levet

    (University of Oxford)

  • Sonia Muliyil

    (University of Oxford)

  • Fangfang Lu

    (University of Oxford)

  • Colin W. Taylor

    (University of Cambridge)

  • Matthew Freeman

    (University of Oxford)

Abstract

The folding capacity of membrane and secretory proteins in the endoplasmic reticulum (ER) can be challenged by physiological and pathological perturbations, causing ER stress. If unresolved, this leads to cell death. We report a role for iRhom pseudoproteases in controlling apoptosis due to persistent ER stress. Loss of iRhoms causes cells to be resistant to ER stress-induced apoptosis. iRhom1 and iRhom2 interact with IP3 receptors, critical mediators of intracellular Ca2+ signalling, and regulate ER stress-induced transport of Ca2+ into mitochondria, a primary trigger of mitochondrial membrane depolarisation and cell death. iRhoms also bind to the anti-apoptotic regulator BCL-2, attenuating the inhibitory interaction between BCL-2 and IP3 receptors, which promotes ER Ca2+ release. The discovery of the participation of iRhoms in the control of ER stress-induced cell death further extends their potential pathological significance to include diseases dependent on protein misfolding and aggregation.

Suggested Citation

  • Iqbal Dulloo & Peace Atakpa-Adaji & Yi-Chun Yeh & Clémence Levet & Sonia Muliyil & Fangfang Lu & Colin W. Taylor & Matthew Freeman, 2022. "iRhom pseudoproteases regulate ER stress-induced cell death through IP3 receptors and BCL-2," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28930-4
    DOI: 10.1038/s41467-022-28930-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28930-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28930-4?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
    ---><---

    References listed on IDEAS

    as
    1. Adam Bartok & David Weaver & Tünde Golenár & Zuzana Nichtova & Máté Katona & Száva Bánsághi & Kamil J. Alzayady & V. Kaye Thomas & Hideaki Ando & Katsuhiko Mikoshiba & Suresh K. Joseph & David I. Yule, 2019. "IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Junji Suzuki & Kazunori Kanemaru & Kuniaki Ishii & Masamichi Ohkura & Yohei Okubo & Masamitsu Iino, 2014. "Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    3. Miao Wang & Randal J. Kaufman, 2016. "Protein misfolding in the endoplasmic reticulum as a conduit to human disease," Nature, Nature, vol. 529(7586), pages 326-335, January.
    4. Nagendra Babu Thillaiappan & Holly A. Smith & Peace Atakpa-Adaji & Colin W. Taylor, 2021. "KRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals," Nature Communications, Nature, vol. 12(1), pages 1-13, 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. Máté Katona & Ádám Bartók & Zuzana Nichtova & György Csordás & Elena Berezhnaya & David Weaver & Arijita Ghosh & Péter Várnai & David I. Yule & György Hajnóczky, 2022. "Capture at the ER-mitochondrial contacts licenses IP3 receptors to stimulate local Ca2+ transfer and oxidative metabolism," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. 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.
    3. Eun-Ji Park & Hyun-Soo Kim & Do-Hyoung Lee & Su-Min Kim & Joon-Sup Yoon & Ji-Min Lee & Se Jin Im & Ho Lee & Min-Woo Lee & Chang-Woo Lee, 2023. "Ssu72 phosphatase is essential for thermogenic adaptation by regulating cytosolic translation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Yu-Jie Chen & Jeffrey Knupp & Anoop Arunagiri & Leena Haataja & Peter Arvan & Billy Tsai, 2021. "PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Roman Nikolaienko & Elisa Bovo & Daniel Kahn & Ryan Gracia & Thomas Jamrozik & Aleksey V. Zima, 2023. "Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR)," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Takuya Kobayashi & Akihisa Tsutsumi & Nagomi Kurebayashi & Kei Saito & Masami Kodama & Takashi Sakurai & Masahide Kikkawa & Takashi Murayama & Haruo Ogawa, 2022. "Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Ara Lee & Gihyun Sung & Sanghee Shin & Song-Yi Lee & Jaehwan Sim & Truong Thi My Nhung & Tran Diem Nghi & Sang Ki Park & Ponnusamy Pon Sathieshkumar & Imkyeung Kang & Ji Young Mun & Jong-Seo Kim & Hyu, 2024. "OrthoID: profiling dynamic proteomes through time and space using mutually orthogonal chemical tools," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Su Jin Ham & Heesuk Yoo & Daihn Woo & Da Hyun Lee & Kyu-Sang Park & Jongkyeong Chung, 2023. "PINK1 and Parkin regulate IP3R-mediated ER calcium release," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Chaiheon Lee & Mingyu Park & W. C. Bhashini Wijesinghe & Seungjin Na & Chae Gyu Lee & Eunhye Hwang & Gwangsu Yoon & Jeong Kyeong Lee & Deok-Ho Roh & Yoon Hee Kwon & Jihyeon Yang & Sebastian A. Hughes , 2024. "Oxidative photocatalysis on membranes triggers non-canonical pyroptosis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Li Qi jun, 2018. "TG could Modulate FPN1 in MES 23.5 Cells by Hepcidin," International Journal of Sciences, Office ijSciences, vol. 7(09), pages 52-55, September.
    11. Kihyoun Park & Hyejin Lim & Jinyoung Kim & Yeseong Hwang & Yu Seol Lee & Soo Han Bae & Hyeongseok Kim & Hail Kim & Shin-Wook Kang & Joo Young Kim & Myung-Shik Lee, 2022. "Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    12. Ariel A. Valiente-Gabioud & Inés Garteizgogeascoa Suñer & Agata Idziak & Arne Fabritius & Jérome Basquin & Julie Angibaud & U. Valentin Nägerl & Sumeet Pal Singh & Oliver Griesbeck, 2023. "Fluorescent sensors for imaging of interstitial calcium," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    13. Fujian Lu & Qing Ma & Wenjun Xie & Carter L. Liou & Donghui Zhang & Mason E. Sweat & Blake D. Jardin & Francisco J. Naya & Yuxuan Guo & Heping Cheng & William T. Pu, 2022. "CMYA5 establishes cardiac dyad architecture and positioning," 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:13:y:2022:i:1:d:10.1038_s41467-022-28930-4. 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.

    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.