| Author |
Zou, Ye Hirschey, Matthew D. Bharathi, Sivakama Ilkayeva, Olga R. Goetzman, Eric S. Otsubo, Chikara Uppala, Radha Zuo, Yi Y. Wang, Dongning Mchugh, Kevin Wang, Jieru Alcorn, John F. |
| Description |
Author Affiliation: Otsubo C ( From the Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224.); Bharathi S ( From the Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224.); Uppala R ( From the Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224.); Ilkayeva OR ( Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27701, and.); Wang D ( Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27701, and.); McHugh K ( From the Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224.); Zou Y ( Department of Mechanical Engineering, University of Hawaii at Manoa, Honolulu, Hawaii 96822.); Wang J ( From the Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224.); Alcorn JF ( From the Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224.); Zuo YY ( Department of Mechanical Engineering, University of Hawaii at Manoa, Honolulu, Hawaii 96822.); Hirschey MD ( Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27701, and.); Goetzman ES ( From the Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224, Eric.goetzman@chp.edu.) |
| Abstract |
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. |
