Adenine nucleotide translocase regulates airway epithelial metabolism, surface hydration and ciliary function
| Autor: | Jennifer M. K. Nguyen, Corrine R. Kliment, Yingze Zhang, Alyssa D. Gregory, Ya-Wen Lu, Venkataramana K. Sidhaye, Frank C. Sciurba, Steven M. Claypool, Douglas N. Robinson, Josiah E. Radder, Mary Jane Kaltreider, Pablo A. Iglesias |
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| Rok vydání: | 2020 |
| Předmět: |
Oxidative phosphorylation
Mitochondrion Dictyostelium discoideum 03 medical and health sciences Pulmonary Disease Chronic Obstructive Downregulation and upregulation Gene expression Humans Dictyostelium Lung 030304 developmental biology 0303 health sciences biology 030302 biochemistry & molecular biology Epithelial Cells Cell Biology respiratory system biology.organism_classification ANT Cell biology respiratory tract diseases Mitochondria Respiratory epithelium Mitochondrial ADP ATP Translocases Homeostasis Research Article |
| Zdroj: | J Cell Sci |
| ISSN: | 1477-9137 |
| Popis: | Airway hydration and ciliary function are critical to airway homeostasis and dysregulated in chronic obstructive pulmonary disease (COPD), which is impacted by cigarette smoking and has no therapeutic options. We utilized a high-copy cDNA library genetic selection approach in the amoeba Dictyostelium discoideum to identify genetic protectors to cigarette smoke. Members of the mitochondrial ADP/ATP transporter family adenine nucleotide translocase (ANT) are protective against cigarette smoke in Dictyostelium and human bronchial epithelial cells. Gene expression of ANT2 is reduced in lung tissue from COPD patients and in a mouse smoking model, and overexpression of ANT1 and ANT2 resulted in enhanced oxidative respiration and ATP flux. In addition to the presence of ANT proteins in the mitochondria, they reside at the plasma membrane in airway epithelial cells and regulate airway homeostasis. ANT2 overexpression stimulates airway surface hydration by ATP and maintains ciliary beating after exposure to cigarette smoke, both of which are key functions of the airway. Our study highlights a potential for upregulation of ANT proteins and/or of their agonists in the protection from dysfunctional mitochondrial metabolism, airway hydration and ciliary motility in COPD. This article has an associated First Person interview with the first author of the paper. |
| Databáze: | OpenAIRE |
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