Adenine Nucleotide Translocase regulates the airway epithelium, mitochondrial metabolism and ciliary function

Abstract

The authors have declared no conflicts of interest exist. AbstractAirway hydration and ciliary function are critical to airway homeostasis and dysregulated in chronic obstructive lung disease (COPD). COPD is the 4 th leading cause of death in the US and is impacted by cigarette smoking with no therapeutic options. We utilized a genetic selection approach in the amoeba Dictyostelium discoideum as a comparative discovery tool in lung biology to identify genetic protectors from cigarette smoke (CS). Adenine nucleotide translocase (ANT), a mitochondrial ADP/ATP transporter, was protective against CS in Dictyostelium and human bronchial epithelial cells. ANT2 gene expression is reduced in lung tissue from COPD patients and in a mouse smoking model. ANT1and ANT2 overexpression resulted in enhanced oxidative respiration and ATP flux. In addition to ANT's presence in the mitochondria, ANT1 and ANT2 reside at the plasma membrane in airway epithelial cells and this localization plays a role in how ANTs regulate airway homeostasis. ANT2 overexpression stimulates airway surface liquid hydration by ATP and maintains ciliary beating after CS exposure, which are key functions of the airway. Our study highlights the potential of ANT modulation in protecting from dysfunctional mitochondrial metabolism, airway hydration, and ciliary motility in COPD.

A Walk in the Memory, from the First Functional Approach up to Its Regulatory Role of Mitochondrial Bioenergetic Flow in Health and Disease: Focus on the Adenine Nucleotide Translocator

“…At this point, we would like to briefly describe one of the latest studies performed by Kliment et al [ 114 ], just to underline how research on ANT is still fervent 30 years after its discovery and also to introduce the ANT2 isoform, which is involved in the development of chronic obstructive pulmonary disease (COPD). The authors observed that ANT2 expression is reduced in lung tissue from patients affected by COPD, and in a mouse smoking model.…”