| First Author | Otsubo C | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 39 | Pages | 23897-904 |
| PubMed ID | 26240137 | Mgi Jnum | J:250422 |
| Mgi Id | MGI:6101886 | Doi | 10.1074/jbc.M115.655837 |
| Citation | Otsubo C, et al. (2015) Long-chain Acylcarnitines Reduce Lung Function by Inhibiting Pulmonary Surfactant. J Biol Chem 290(39):23897-904 |
| abstractText | The role of mitochondrial energy metabolism in maintaining lung function is not understood. We previously observed reduced lung function in mice lacking the fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD). Here, we demonstrate that long-chain acylcarnitines, a class of lipids secreted by mitochondria when metabolism is inhibited, accumulate at the air-fluid interface in LCAD(-/-) lungs. Acylcarnitine accumulation is exacerbated by stress such as influenza infection or by dietary supplementation with l-carnitine. Long-chain acylcarnitines co-localize with pulmonary surfactant, a unique film of phospholipids and proteins that reduces surface tension and prevents alveolar collapse during breathing. In vitro, the long-chain species palmitoylcarnitine directly inhibits the surface adsorption of pulmonary surfactant as well as its ability to reduce surface tension. Treatment of LCAD(-/-) mice with mildronate, a drug that inhibits carnitine synthesis, eliminates acylcarnitines and improves lung function. Finally, acylcarnitines are detectable in normal human lavage fluid. Thus, long-chain acylcarnitines may represent a risk factor for lung injury in humans with dysfunctional fatty acid oxidation. |
