B109-03 Flavored Electronic Cigarette Aerosol Induces Mitochondrial Dysfunction in Human Primary Alveolar Type II Cells

Rationale E-cigarettes contain various flavorings and nicotine. They can induce the alveolar epithelium injury and contribute to lung dysfunction. ATII cells have stem cell potential, produce, and secrete pulmonary surfactants, indicating their critical role in the lung. They are abundant in mitochondria, which are required to meet their high energy demands. DJ-1 is a multifunctional protein with a cytoprotective role, localized in mitochondria. Methods ATII cells were isolated from non-smoker organ donors whose lungs were unsuitable for transplantation and were donated for biomedical research. Precision-cut lung slices (PCLS) were also generated. Moreover, DJ-1 KO mice were used to study ATII cell function. Human ATII cells, PCLS, and mice were exposed to e-cigarette aerosols containing cinnamon roll flavor with or without nicotine. Also, plasma was obtained from e-cigarette users for this study. Results Our data indicate mitochondrial dysfunction, evidenced by decreased electron transport chain activity, increased MitoClox levels, and mitochondrial DNA damage in ATII cells and PCLS. Additionally, this exposure reduced the levels of UQCRC2 and NDUFS1 in human ATII cells as detected by immunofluorescence. Cinnamon roll with nicotine e-cigarette aerosols affected mitochondrial ROS levels in a DJ-1-mediated manner in vitro. Furthermore, an increase in LAMP2 and LC3B was observed in ATII cells treated with cinnamon-roll e-cigarette aerosols containing nicotine by immunofluorescence, indicating autophagy. E-cigarette users had increased mitochondrial DNA damage in plasma. Our findings indicated decreased SP-C expression in ATII cells in DJ-1 KO mice exposed to e-cigarette aerosols. Also, the impaired mitochondrial respiratory chain complexes I and III were decreased in murine ATII cells. Conclusions Our results demonstrate that cinnamon roll with nicotine e-cigarette aerosols caused mitochondrial dysfunction. These alterations affected the interaction between the cytosol and mitochondria and contributed to ATII cell death. This abstract is funded by: NIH