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  3. Alterations in the molecular regulation of mitochondrial metabolism in human alveolar epithelial cells in response to cigarette- and heated tobacco product emissions

Alterations in the molecular regulation of mitochondrial metabolism in human alveolar epithelial cells in response to cigarette- and heated tobacco product emissions

  • Toxicol Lett. 2024 Nov:401:89-100. doi: 10.1016/j.toxlet.2024.09.004.
Michele Davigo 1,  Frederik Jan Van Schooten 2,  Bas Wijnhoven 2,  Marie Jose Drittij 2,  Ludwig Dubois 3,  Antoon Opperhuizen 4,  Reinskje Talhout 5,  Alexander H V Remels 2
Affiliations

Affiliations

  • 1 School of Nutrition and Translational Research in Metabolism (NUTRIM), Department of Pharmacology and Toxicology, Maastricht University Medical Center+, Maastricht, the Netherlands; Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, Bilthoven 3720 BA, the Netherlands. Electronic address: m.davigo@maastrichtuniversity.nl.
  • 2 School of Nutrition and Translational Research in Metabolism (NUTRIM), Department of Pharmacology and Toxicology, Maastricht University Medical Center+, Maastricht, the Netherlands.
  • 3 The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
  • 4 School of Nutrition and Translational Research in Metabolism (NUTRIM), Department of Pharmacology and Toxicology, Maastricht University Medical Center+, Maastricht, the Netherlands; Office of Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, the Netherlands.
  • 5 Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, Bilthoven 3720 BA, the Netherlands.
PMID: 39284537 DOI: 10.1016/j.toxlet.2024.09.004
Abstract

Mitochondrial abnormalities in lung epithelial cells have been associated with chronic obstructive pulmonary disease (COPD) pathogenesis. Cigarette smoke (CS) can induce alterations in the molecular pathways regulating mitochondrial function in lung epithelial cells. Recently, heated tobacco products (HTPs) have been marketed as harm reduction products compared with regular cigarettes. However, the effects of HTP emissions on human alveolar epithelial cell metabolism and on the molecular mechanisms regulating mitochondrial content and function are unclear. In this study, human alveolar epithelial cells (A549) were exposed to cigarette or HTP emissions in the form of liquid extracts. The oxygen consumption rate of differently exposed cells was measured, and mRNA and protein abundancy of key molecules involved in the molecular regulation of Mitochondrial Metabolism were assessed. Furthermore, we used a Mitophagy detection probe to visualize mitochondrial breakdown over time in response to the extracts. Both types of extracts induced increases in basal-, maximal- and spare respiratory capacity, as well as in cellular ATP production. Moreover, we observed alterations in the abundancy of regulatory molecules controlling mitochondrial biogenesis and Mitophagy. Mitophagy was not significantly altered in response to the extracts, as no significant differences compared to vehicle-treated cells were observed.

Keywords

Chronic obstructive pulmonary disease; Cigarette smoke; Heated tobacco products; Human alveolar epithelial cells; Mitochondrial biogenesis; Mitophagy; Oxygen consumption rate.

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