{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:45:17Z","timestamp":1789497917708,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T00:00:00Z","timestamp":1653696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commission on Funding for Junior Scientists and Researchers, Medical Faculty, Otto-von-Guericke University Magdeburg","award":["361210922\/RTG 2408"],"award-info":[{"award-number":["361210922\/RTG 2408"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["361210922\/RTG 2408"],"award-info":[{"award-number":["361210922\/RTG 2408"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Food and Consumer Product Safety Authority (NVWA)","award":["361210922\/RTG 2408"],"award-info":[{"award-number":["361210922\/RTG 2408"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mitochondrial functionality is crucial for the execution of physiologic functions of metabolically active cells in the respiratory tract including airway epithelial cells (AECs). Cigarette smoke is known to impair mitochondrial function in AECs. However, the potential contribution of mitochondrial dysfunction in AECs to airway infection and airway epithelial barrier dysfunction is unknown. In this study, we used an in vitro model based on AECs exposed to cigarette smoke extract (CSE) followed by an infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress as an indicator of mitochondrial stress were quantified upon CSE and Sp treatment. In addition, expression of proteins associated with mitophagy, mitochondrial content, and biogenesis as well as mitochondrial fission and fusion was quantified. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with indices of mitochondrial function. We observed that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp.<\/jats:p>","DOI":"10.3390\/cells11111771","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:50:51Z","timestamp":1653814251000},"page":"1771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-3423","authenticated-orcid":false,"given":"Mahyar","family":"Aghapour","sequence":"first","affiliation":[{"name":"Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, 39120 Magdeburg, Germany"},{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2537-3036","authenticated-orcid":false,"given":"Christy B. M.","family":"Tulen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-6474","authenticated-orcid":false,"given":"Mohsen","family":"Abdi Sarabi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology and Angiology, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7201-0836","authenticated-orcid":false,"given":"S\u00f6nke","family":"Weinert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology and Angiology, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"M\u00fcsken","sequence":"additional","affiliation":[{"name":"Central Facility for Microscopy, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borna","family":"Relja","sequence":"additional","affiliation":[{"name":"Experimental Radiology, Department of Radiology and Nuclear Medicine, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik-Jan","family":"van Schooten","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Jeron","sequence":"additional","affiliation":[{"name":"Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, 39120 Magdeburg, Germany"},{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"Braun-Dullaeus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology and Angiology, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander H.","family":"Remels","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Bruder","sequence":"additional","affiliation":[{"name":"Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, 39120 Magdeburg, Germany"},{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1165\/rcmb.2017-0200TR","article-title":"Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease: Role of cigarette smoke exposure","volume":"58","author":"Aghapour","year":"2018","journal-title":"Am. 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