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

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, intranas

SUBMITTER: Islam MN 

PROVIDER: S-EPMC9529882 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature