E-cigarette-induced changes in cell stress and mitochondrial function

• Published in: Free radical biology & medicine Vol. 228; pp. 329 - 338
• Main Authors: Chitteti, Ramamurthy, Zuniga-Hertz, Juan Pablo, Masso-Silva, Jorge A., Shin, John, Niesman, Ingrid, Bojanowski, Christine M., Kumar, Avnee J., Hepokoski, Mark, Crotty Alexander, Laura E, Patel, Hemal H, Roth, David M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.02.2025
• Subjects: Adult; DNA, Mitochondrial - genetics; Electronic (e)-cigarette; Electronic Nicotine Delivery Systems; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Exosomes - drug effects; Exosomes - metabolism; Female; Humans; Male; Membrane Potential, Mitochondrial - drug effects; Metabolic stress; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Nicotine - adverse effects; Oxidative Stress - drug effects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tobacco; Vaping - adverse effects; Young Adult; Tobacco; Mitochondria; Reactive oxygen species; Epithelial cells; Electronic (e)-cigarette; Metabolic stress; Endothelial cells
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2025.01.004

Inhaling aerosols from electronic nicotine delivery systems, such as e-cigarettes (e-cigs), may pose health risks beyond those caused by nicotine intake. Exposure to e-cig aerosols can lead to the release of exosomes and metabolites into the bloodstream, potentially affecting mitochondrial physiology across the body, leading to chronic inflammatory diseases. In this study we assessed the effects of e-cig use by young healthy human subjects on the circulating exosome profile and markers of cell stress, and also defined the effects of e-cig user plasma on mitochondrial function in endothelial cells (EA. Hy 926) and epithelial cells (A549) via adoptive transfer. E-cig users had altered plasma exosome profiles, with significantly increased levels of cell free mitochondrial DNA (mtDNA), protein carbonyls, and 4-HNE relative to non-users. Plasma from e-cig users decreased maximal mitochondrial respiration and spare capacity of cells, while also increasing metabolic stress, as evidenced by changes in mitochondrial phenotype from basal to stressed in both endothelial and epithelial cells, which was corroborated by electron microscopy demonstrating structural changes in mitochondria. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels significantly increased in e-cig plasma-subjected cells. Overall, we identified alterations in plasma exosome profiles and increased markers of mitochondrial stress in e-cig users and evidence that circulating factors within plasma from e-cig users drives metabolic stress in endothelial and epithelial cells. Our results imply that e-cig use adversely affects mitochondrial function, leading to stress and potentially chronic inflammation across the body. Inhalation of e-cigarette aerosols alters circulating nanoparticles in e-cigarette users. Factors within e-cig user plasma change metabolism within endothelial and epithelial cells, which may be primarily due to oxidative stress. [Display omitted] •E-cig use induces stress both in human subjects and cell culture models.•E-cig users show significantly higher plasma mitochondrial DNA than non-users.•E-cig plasma exposure alters respiration, stressing epithelial and endothelial cells.