IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33543-y.html
   My bibliography  Save this article

The mitochondrial calcium uniporter of pulmonary type 2 cells determines severity of acute lung injury

Author

Listed:
  • Mohammad Naimul Islam

    (Columbia University)

  • Galina A. Gusarova

    (Columbia University)

  • Shonit R. Das

    (Columbia University)

  • Li Li

    (Columbia University)

  • Eiji Monma

    (Columbia University)

  • Murari Anjaneyulu

    (Columbia University)

  • Liberty Mthunzi

    (Columbia University)

  • Sadiqa K. Quadri

    (Columbia University)

  • Edward Owusu-Ansah

    (Columbia University)

  • Sunita Bhattacharya

    (Columbia University)

  • Jahar Bhattacharya

    (Columbia University
    Columbia University)

Abstract

Acute Lung Injury (ALI) due to inhaled pathogens causes high mortality. Underlying mechanisms are inadequately understood. Here, by optical imaging of live mouse lungs we show that a key mechanism is the viability of cytosolic Ca2+ buffering by the mitochondrial Ca2+ uniporter (MCU) in the lung’s surfactant-secreting, alveolar type 2 cells (AT2). The buffering increased mitochondrial Ca2+ and induced surfactant secretion in wild-type mice, but not in mice with AT2-specific MCU knockout. In the knockout mice, ALI due to intranasal LPS instillation caused severe pulmonary edema and mortality, which were mitigated by surfactant replenishment prior to LPS instillation, indicating surfactant’s protective effect against alveolar edema. In wild-type mice, intranasal LPS, or Pseudomonas aeruginosa decreased AT2 MCU. Loss of MCU abrogated buffering. The resulting mortality was reduced by spontaneous recovery of MCU expression, or by MCU replenishment. Enhancement of AT2 mitochondrial buffering, hence endogenous surfactant secretion, through MCU replenishment might be a therapy against ALI.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33543-y
    DOI: 10.1038/s41467-022-33543-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33543-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33543-y?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. A. Phillip West & Igor E. Brodsky & Christoph Rahner & Dong Kyun Woo & Hediye Erdjument-Bromage & Paul Tempst & Matthew C. Walsh & Yongwon Choi & Gerald S. Shadel & Sankar Ghosh, 2011. "TLR signalling augments macrophage bactericidal activity through mitochondrial ROS," Nature, Nature, vol. 472(7344), pages 476-480, April.
    3. 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.
    4. Alyssa A. Lombardi & Andrew A. Gibb & Ehtesham Arif & Devin W. Kolmetzky & Dhanendra Tomar & Timothy S. Luongo & Pooja Jadiya & Emma K. Murray & Pawel K. Lorkiewicz & György Hajnóczky & Elizabeth Murp, 2019. "Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    5. Kristin Westphalen & Galina A. Gusarova & Mohammad N. Islam & Manikandan Subramanian & Taylor S. Cohen & Alice S. Prince & Jahar Bhattacharya, 2014. "Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity," Nature, Nature, vol. 506(7489), pages 503-506, February.
    6. Larry L. Luchsinger & Mariana Justino de Almeida & David J. Corrigan & Melanie Mumau & Hans-Willem Snoeck, 2016. "Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential," Nature, Nature, vol. 529(7587), pages 528-531, January.
    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. 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. 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.
    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. Jawaher Alharthi & Ali Bayoumi & Khaled Thabet & Ziyan Pan & Brian S. Gloss & Olivier Latchoumanin & Mischa Lundberg & Natalie A. Twine & Duncan McLeod & Shafi Alenizi & Leon A. Adams & Martin Weltman, 2022. "A metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes," Nature Communications, Nature, vol. 13(1), pages 1-19, 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. Sanghyeon Choi & Youngjin Lee & Shinhye Park & Song Yee Jang & Jongbin Park & Do Won Oh & Su-Man Kim & Tae-Hwan Kim & Ga Seul Lee & Changyi Cho & Byoung Sik Kim & Donghan Lee & Eun-Hee Kim & Hae-Kap C, 2024. "Dissemination of pathogenic bacteria is reinforced by a MARTX toxin effector duet," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    8. Lindsay McGregor & Samira Acajjaoui & Ambroise Desfosses & Melissa Saïdi & Maria Bacia-Verloop & Jennifer J. Schwarz & Pauline Juyoux & Jill Velsen & Matthew W. Bowler & Andrew A. McCarthy & Eaazhisai, 2023. "The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Shuai Gao & Lingyu Gao & Dailin Yuan & Xu’ai Lin & Stijn Veen, 2024. "Gonococcal OMV-delivered PorB induces epithelial cell mitophagy," Nature Communications, Nature, vol. 15(1), pages 1-15, 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. Xudong Wang & Siyu Su & Yuqing Zhu & Xiaolong Cheng & Chen Cheng & Leilei Chen & Anhua Lei & Li Zhang & Yuyan Xu & Dan Ye & Yi Zhang & Wei Li & Jin Zhang, 2023. "Metabolic Reprogramming via ACOD1 depletion enhances function of human induced pluripotent stem cell-derived CAR-macrophages in solid tumors," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Michal Scur & Ahmad Bakur Mahmoud & Sayanti Dey & Farah Abdalbarri & Iona Stylianides & Daniel Medina-Luna & Gayani S. Gamage & Aaron Woblistin & Alexa N. M. Wilson & Haggag S. Zein & Ashley Stueck & , 2022. "Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    13. Clive Drakeford & Sonia Aguila & Fiona Roche & Karsten Hokamp & Judicael Fazavana & Mariana P. Cervantes & Annie M. Curtis & Heike C. Hawerkamp & Sukhraj Pal Singh Dhami & Hugo Charles-Messance & Emer, 2022. "von Willebrand factor links primary hemostasis to innate immunity," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    14. 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.
    15. Lulu Ren & Jianqin Wan & Xiaoyan Li & Jie Yao & Yan Ma & Fanchao Meng & Shusen Zheng & Weidong Han & Hangxiang Wang, 2024. "Mitochondrial rewiring with small-molecule drug-free nanoassemblies unleashes anticancer immunity," Nature Communications, Nature, vol. 15(1), pages 1-20, 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_s41467-022-33543-y. 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.