Long-chain Acylcarnitines Reduce Lung Function by Inhibiting Pulmonary Surfactant.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Otsubo, C; Bharathi, S; Uppala, R; Ilkayeva, OR; Wang, D; McHugh, K; Zou, Y; Wang, J; Alcorn, JF; Zuo, YY; Hirschey, MD; Goetzman, ES

Published Date

  • September 25, 2015

Published In

Volume / Issue

  • 290 / 39

Start / End Page

  • 23897 - 23904

PubMed ID

  • 26240137

Pubmed Central ID

  • PMC4583047

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M115.655837


  • eng

Conference Location

  • United States