Cell Biology

Keeping Things Clear

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Science  08 Oct 2010:
Vol. 330, Issue 6001, pp. 152-153
DOI: 10.1126/science.330.6001.152-c

Atp8b1 (red) at the cell surface (green) in a mouse lung.

CREDIT: RAY ET AL., NAT. MED. 16, 10.1038/NM.2213 (2010)

Pneumonia is a serious inflammatory lung disease commonly caused by bacterial infection. It is a major cause of death in all age groups and particularly in those who are chronically ill, and further insight into its pathogenesis may promote the development of new therapeutic approaches. Ray et al. have discovered an alternative mechanism underlying the pathobiology of pneumonia caused by bacterial infection. Cardiolipin is a phospholipid that mitochondrial membranes are rich in. It is a minor component of pulmonary surfactant, which is secreted into the airways and lines the alveolar surface of the lungs, reducing surface tension and enabling proper lung function. Higher concentrations of cardiolipin are found in animal models of lung injury, suggesting that its regulation is important in disease pathogenesis. After discovering higher levels of cardiolipin in fluid isolated from the lungs of pneumonia patients, the authors uncovered a critical role for cardiolipin in surfactant activity and in lung structure and function in mice. The extracellular levels of cardiolipin are regulated by the lipid transporter Atp8b1, which imports phospholipids across the plasma membrane. Mutants of Atp8b1 are found in a familial disorder associated with an increased risk of pneumonia. Indeed, by overexpression and loss-of-function studies in cultured cells and in mice, the authors established a critical role for Atp8b1. These results suggest that the clearance of cardiolipin from the lungs may be of therapeutic benefit for treating pneumonia caused by bacteria, and thus could help to alleviate the current dependence on broad-spectrum antibiotics, which has led to the emergence of dangerous drug-resistant strains.

Nat. Med. 16, 10.1038/nm.2213 (2010).

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