The mitochondrial calcium uniporter of pulmonary type 2 cells determines severity of acute lung injury
Year: 2022
Type: 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 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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Awards: G1181017599, Genetic Dissection of OXPHOS Assembly in Skeletal Muscles, G247499674, G2535263842, Mitochondrial dynamics in acute lung injury, G382402740, G4390587119, BD Biosciences Influx, Identifying Remote Regulators of Complex I Biogenesis in Drosophila, MICROPUNCTURE STUDIES OF LUNG WATER AND SOLUTE EXCHANGE, G687964168, NOVEL MECHANISMS OF ALVEOLAR INFLAMMATION., Mechanistic role of membrane pore formation in lung-endothelial barrier failure due to blood-borne pathogens.
OpenAlex ID: W4300594239