November/December 2020 ARTICLE - DR. JINMING ZHAO AND DR. SALLY WENZEL
APEBP1 acts as a rheostat between prosurvival autophagy and ferroptotic death in ashmatic epithelial cells
Airway epithelial cells are increasingly recognized as abnormal in asthma, particularly in Type-2 High Asthma. A recent study from Zhao et al identified a novel regulatory mechanism involving the autophagic protein LC3 interacting with ferroptotic machinery (15 lipoxygenase and phosphatidylethanolamine binding protein-1) and its activation to limit ferroptotic cell death and release of mitochdondrial DNA (mtDNA) in in vitro model systems. These results were reflected ex vivo in fresh asthmatic airway epithelial cells showing lower airway mtDNA levels in association with worsening asthma. These studies suggest that asthmatic airway epithelial cells are in a level of heightened stress, potentially more susceptible to subtle increases in oxidative stress or other factors, which overwhelm the autophagic/mitophagic process to promote cell death, inflammation and potentially asthma exacerbations. Thus, targeting the ferroptotic machinery could reverse these effects and improve asthma outcomes.
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