Mitochondrial fusion in the pathogenesis of severe asthma with fungal sensitization

So Ri Kim, Yong Chul Lee, Hae Jin Park, Dong Im Kim, Soon Ha Kim


Mitochondria are dynamic organelles that undergo fission and fusion events. Under persistent stressful condition, the balance between fission and fusion of mitochondria is out of control. However, there is little information on mitochondrial dynamics in the pathogenesis of fungus-induced allergic asthma. In this study, we aimed to evaluate the morphologic changes of mitochondria in airway inflammatory cells from a murine model of bronchial asthma. The mice sensitized and challenged with Aspergillus fumigatus (Af) showed the typical features of bronchial asthma. Interestingly, these asthmatic features were refractory to the treatment with oral dexamethasone, whereas they were improved significantly by the administration of mitochondrial ROS inhibitor, NecroX-7. In addition, electron-microscopic analysis revealed that in BAL cells from Af-inhaled mice, the mitochondria were dramatically elongated, fused each other compared to the finding of cells from control mice. The levels of mitofusin1 and mitofusin2 were significantly increased in lung tissues of Af-inhaled mice. Administration of dexamethasone, a current representative therapeutic agent for bronchial asthma, did not affect the increases in mitofusin1 and mitofusin2 levels and morphological changes, but NecroX-7 decreased the expression of mitofusin1 and mitofusin2 and restored the morphology of mitochondria. These findings indicate that the mitochondrial hyper-fusion may be induced by fungal allergen stimulation in airway inflammatory cells and it can be one of the molecular mechanisms for the pathogenesis of steroid-resistant allergic airway inflammation.


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European Respiratory Society 2016
    • ERS 26th (2016)