AI Article Synopsis
- Acute Lung Injury (ALI) from inhaled pathogens leads to high mortality, and the mechanisms behind it are not well understood.
- Optical imaging studies in live mice reveal that the mitochondrial Ca uniporter (MCU) plays a crucial role in calcium buffering within alveolar type 2 cells, which is linked to surfactant secretion.
- Mice without MCU show severe lung damage and death after exposure to harmful substances, but providing surfactant beforehand helps protect against these effects, suggesting that boosting MCU function could be a potential treatment for ALI.
Article 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 Ca buffering by the mitochondrial Ca uniporter (MCU) in the lung's surfactant-secreting, alveolar type 2 cells (AT2). The buffering increased mitochondrial Ca 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529882 | PMC |
| http://dx.doi.org/10.1038/s41467-022-33543-y | DOI Listing |
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