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2-Chloro and 2-Bromopalmitic Acids inhibit mitochondrial Function in Airway epithelial cells

Karina Ricart1, Kyle S. McCommis2,3, David A. Ford 2,3,* and Rakesh P. Patel1,*.

1Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 63104, USA
3Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA
*Correspondence: David Ford david.ford@health.slu.edu or rakeshpatel@uabmc.edu

DOI: https://doi.org/10.22427/NTP-DATA-501-002-001-000-9

Publication

Abstract

2-Chloropalmitic acid (2-ClPA) and 2-bromopalmitic acid (2-BrPa) increase in inflammatory lung disease associated with formation of hypochlorous or hypobromous acid, and exposure to halogen gases. Moreover, these lipids may elicit cell responses that contribute to lung injury, but the mechanisms remain unclear. Here, we tested the hypothesis that 2-ClPA and 2-BrPA induce metabolic defects in airway epithelial cells by targeting mitochondria. H441 or primary human airway epithelial cells were treated with 2-ClPA or 2-BrPA and bioenergetics measured using oxygen consumption rates and extracellular acidification rates, as well as respiratory complex activities. Relative to vehicle or palmitic acid, both 2-halofatty acids in-hibited ATP-linked oxygen consumption and reserve capacity, suggestive of increased proton leak. However, neither 2-ClPA nor 2-BrPA altered mitochondrial membrane potential, suggesting proton leak does not underlie inhibited ATP-linked oxygen consumption. Interestingly, complex II activity was significantly inhibited which may contribute to diminished reserve capacity, but activity of complexes I, III and IV remain unchanged. Taken together, the presented data highlight the potential of 2-halofatty acids to disrupt bioenergetics and in turn cause cellular dysfunction.

Keywords: Chlorinated lipids; Brominated lipids; Mitochondrial respiration

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