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

Author

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  • 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
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    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. 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.
    4. 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.
    5. 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.
    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.
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