Senior Vice Chancellor's Research Seminar

Topic Overview:

Airway hydration and ciliary function are biological processes that are critical to airway homeostasis and are dysregulated in several diseases, notably chronic bronchitis and chronic obstructive lung disease (COPD). COPD is the third leading cause of death in the United States and is affected by cigarette smoking, with no therapeutic options that reverse pathogenesis or mortality. To identify new relevant pathways, Kliment and colleagues used the amoeba Dictyostelium discoideum as a novel comparative discovery tool for lung biology and identified adenine nucleotide translocase (ANT), a canonical mitochondrial ADP/ATP transporter, as being protective against cigarette smoke in Dictyostelium and human bronchial epithelial cells. In addition to mitochondria, populations of ANT1 and ANT2 may reside at the apical plasma membrane and motile cilia in airway epithelia. At the plasma membrane, ANT2 stimulates an increase in airway surface liquid hydration that is mediated via ATP. ANT2 also protects ciliary beat frequency from the negative affect of cigarette smoke in primary human ciliated airway epithelial cultures. ANT2 gene expression is reduced in lung tissue from COPD patients and in a mouse model of COPD, suggesting ANT2 may be associated with COPD pathogenesis. These findings further highlight the potential of ANT2 modulation in protecting from metabolic defects, airway hydration, ATP regulation, and ciliary motility defects, thereby maintaining airway homeostasis. Overall, combining the benefits of two model systems, human lung epithelium and Dictyostelium, provides a powerful approach for discovering new lung and airway biology, while potentiating novel strategies for developing innovative therapies. The unexpected role of ANT in ciliary function may provide the clue about a key missing link in the regulation of airway surface hydration, which is essential for many airway diseases, including COPD. Kliment and colleagues have also become very interested in the role of ANT in cell fate, specifically in mitochondrial homeostasis, mitophagy, and cellular senescence in lung disease.

Continuing Medical Education (CME) credit: To receive CME credit for this lecture, text the code COGPOR to 412-312-4424 within 24 hours of the session’s start. (Your mobile phone number first must be linked to your account at cce.upmc.com.) You can also email kbg12@pitt.edu to receive credit for this session.






							Topic Overview: Airway hydration and ciliary function are biological processes that are critical to airway homeostasis and are dysregulated in several diseases, notably chronic bronchitis and chronic obstructive lung disease (COPD). COPD is the third leading cause of death in the United States and is affected by cigarette smoking, with no therapeutic options that reverse pathogenesis or mortality. To identify new relevant pathways, Kliment and colleagues used the amoeba Dictyostelium discoideum as a novel comparative discovery tool for lung biology and identified adenine nucleotide translocase (ANT), a canonical mitochondrial ADP/ATP transporter, as being protective against cigarette smoke in Dictyostelium and human bronchial epithelial cells. In addition to mitochondria, populations of ANT1 and ANT2 may reside at the apical plasma membrane and motile cilia in airway epithelia. At the plasma membrane, ANT2 stimulates an increase in airway surface liquid hydration that is mediated via ATP. ANT2 also protects ciliary beat frequency from the negative affect of cigarette smoke in primary human ciliated airway epithelial cultures. ANT2 gene expression is reduced in lung tissue from COPD patients and in a mouse model of COPD, suggesting ANT2 may be associated with COPD pathogenesis. These findings further highlight the potential of ANT2 modulation in protecting from metabolic defects, airway hydration, ATP regulation, and ciliary motility defects, thereby maintaining airway homeostasis. Overall, combining the benefits of two model systems, human lung epithelium and Dictyostelium, provides a powerful approach for discovering new lung and airway biology, while potentiating novel strategies for developing innovative therapies. The unexpected role of ANT in ciliary function may provide the clue about a key missing link in the regulation of airway surface hydration, which is essential for many airway diseases, including COPD. Kliment and colleagues have also become very interested in the role of ANT in cell fate, specifically in mitochondrial homeostasis, mitophagy, and cellular senescence in lung disease. Continuing Medical Education (CME) credit: To receive CME credit for this lecture, text the code COGPOR to 412-312-4424 within 24 hours of the session’s start. (Your mobile phone number first must be linked to your account at cce.upmc.com.) You can also email kbg12@pitt.edu to receive credit for this session.