IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48055-0.html
   My bibliography  Save this article

Fatal COVID-19 pulmonary disease involves ferroptosis

Author

Listed:
  • Baiyu Qiu

    (Columbia University)

  • Fereshteh Zandkarimi

    (Columbia University
    Columbia University)

  • Anjali Saqi

    (Columbia University Irving Medical Center)

  • Candace Castagna

    (Columbia University Irving Medical Center)

  • Hui Tan

    (Columbia University)

  • Miroslav Sekulic

    (Columbia University Irving Medical Center)

  • Lisa Miorin

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Hanina Hibshoosh

    (Columbia University Irving Medical Center)

  • Shinya Toyokuni

    (Nagoya University Graduate School of Medicine
    Nagoya University)

  • Koji Uchida

    (The University of Tokyo)

  • Brent R. Stockwell

    (Columbia University
    Columbia University Irving Medical Center
    Columbia University)

Abstract

SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.

Suggested Citation

  • Baiyu Qiu & Fereshteh Zandkarimi & Anjali Saqi & Candace Castagna & Hui Tan & Miroslav Sekulic & Lisa Miorin & Hanina Hibshoosh & Shinya Toyokuni & Koji Uchida & Brent R. Stockwell, 2024. "Fatal COVID-19 pulmonary disease involves ferroptosis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48055-0
    DOI: 10.1038/s41467-024-48055-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48055-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-48055-0?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. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "Author Correction: A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 598(7882), pages 2-2, October.
    2. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 595(7865), pages 114-119, July.
    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. Dhiraj K. Singh & Ekaterina Aladyeva & Shibali Das & Bindu Singh & Ekaterina Esaulova & Amanda Swain & Mushtaq Ahmed & Journey Cole & Chivonne Moodley & Smriti Mehra & Larry S. Schlesinger & Maxim N. , 2022. "Myeloid cell interferon responses correlate with clearance of SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Xiaolei Wang & Terrence Tsz-Tai Yuen & Ying Dou & Jingchu Hu & Renhao Li & Zheng Zeng & Xuansheng Lin & Huarui Gong & Celia Hoi-Ching Chan & Chaemin Yoon & Huiping Shuai & Deborah Tip-Yin Ho & Ivan Fa, 2023. "Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Xin Pan & Lan Wang & Juntang Yang & Yingge Li & Min Xu & Chenxi Liang & Lulu Liu & Zhongzheng Li & Cong Xia & Jiaojiao Pang & Mengyuan Wang & Meng Li & Saiya Guo & Peishuo Yan & Chen Ding & Ivan O. Ro, 2024. "TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Aleksandr Ianevski & Anil K. Giri & Tero Aittokallio, 2022. "Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Laura Heydemann & Małgorzata Ciurkiewicz & Georg Beythien & Kathrin Becker & Klaus Schughart & Stephanie Stanelle-Bertram & Berfin Schaumburg & Nancy Mounogou-Kouassi & Sebastian Beck & Martin Zickler, 2023. "Hamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Guangyuan Li & Baobao Song & Harinder Singh & V. B. Surya Prasath & H. Leighton Grimes & Nathan Salomonis, 2023. "Decision level integration of unimodal and multimodal single cell data with scTriangulate," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Jingyang Qian & Jie Liao & Ziqi Liu & Ying Chi & Yin Fang & Yanrong Zheng & Xin Shao & Bingqi Liu & Yongjin Cui & Wenbo Guo & Yining Hu & Hudong Bao & Penghui Yang & Qian Chen & Mingxiao Li & Bing Zha, 2023. "Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Kuei-Pin Chung & Chih-Ning Cheng & Yi-Jung Chen & Chia-Lang Hsu & Yen-Lin Huang & Min-Shu Hsieh & Han-Chun Kuo & Ya-Ting Lin & Yi-Hsiu Juan & Kiichi Nakahira & Yen-Fu Chen & Wei-Lun Liu & Sheng-Yuan R, 2024. "Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    9. Benjamin Ng & Kevin Y. Huang & Chee Jian Pua & Sivakumar Viswanathan & Wei-Wen Lim & Fathima F. Kuthubudeen & Yu-Ning Liu & An An Hii & Benjamin L. George & Anissa A. Widjaja & Enrico Petretto & Stuar, 2024. "Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Minzhe Guo & Michael P. Morley & Cheng Jiang & Yixin Wu & Guangyuan Li & Yina Du & Shuyang Zhao & Andrew Wagner & Adnan Cihan Cakar & Michal Kouril & Kang Jin & Nathan Gaddis & Joseph A. Kitzmiller & , 2023. "Guided construction of single cell reference for human and mouse lung," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Maik Pietzner & Robert Lorenz Chua & Eleanor Wheeler & Katharina Jechow & Julian D. S. Willett & Helena Radbruch & Saskia Trump & Bettina Heidecker & Hugo Zeberg & Frank L. Heppner & Roland Eils & Mar, 2022. "ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Praveen Weeratunga & Laura Denney & Joshua A. Bull & Emmanouela Repapi & Martin Sergeant & Rachel Etherington & Chaitanya Vuppussetty & Gareth D. H. Turner & Colin Clelland & Jeongmin Woo & Amy Cross , 2023. "Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    13. Rachel Erickson & Chang Huang & Cameron Allen & Joanna Ireland & Gwynne Roth & Zhongcheng Zou & Jinghua Lu & Bernard A. P. Lafont & Nicole L. Garza & Beniah Brumbaugh & Ming Zhao & Motoshi Suzuki & Li, 2023. "SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    15. Leila R. Martins & Lina Sieverling & Michelle Michelhans & Chiara Schiller & Cihan Erkut & Thomas G. P. Grünewald & Sergio Triana & Stefan Fröhling & Lars Velten & Hanno Glimm & Claudia Scholl, 2024. "Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    16. Christina Beck & Deepak Ramanujam & Paula Vaccarello & Florenc Widenmeyer & Martin Feuerherd & Cho-Chin Cheng & Anton Bomhard & Tatiana Abikeeva & Julia Schädler & Jan-Peter Sperhake & Matthias Graw &, 2023. "Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Pablo Jané & Xiaoying Xu & Vincent Taelman & Eduardo Jané & Karim Gariani & Rebecca A. Dumont & Yonathan Garama & Francisco Kim & María Val Gomez & Martin A. Walter, 2023. "The Imageable Genome," Nature Communications, Nature, vol. 14(1), pages 1-15, 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_s41467-024-48055-0. 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.