{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:10:40Z","timestamp":1760677840930,"version":"build-2065373602"},"reference-count":123,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"National Agency for the Promotion of Science and Technology (ANPCYT), Argentina","doi-asserted-by":"publisher","award":["PICT-2018-77204429","PICT-2015-1031","PICT-2020 SERIE A-03854"],"award-info":[{"award-number":["PICT-2018-77204429","PICT-2015-1031","PICT-2020 SERIE A-03854"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"National Scientific and Technical Research Council","doi-asserted-by":"crossref","award":["PIP 2015\u20132017 11220150100227CO","PIP 2022\u20132024 11220210100990CO"],"award-info":[{"award-number":["PIP 2015\u20132017 11220150100227CO","PIP 2022\u20132024 11220210100990CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Pontifical Catholic University of Argentina","award":["PI CyT UCA-2024 800 202403 00001 CT"],"award-info":[{"award-number":["PI CyT UCA-2024 800 202403 00001 CT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene, which encodes a cAMP-activated chloride channel essential for epithelial function. Beyond its canonical role, evidence suggests CFTR also influences mitochondrial function. Previous studies have identified CFTR- and Cl-dependent genes, including MTND4 and CISD1, which are downregulated in CF cells and play a critical role in mitochondrial function. CF cells exhibit altered mitochondrial complex I (mCx-I) activity and impaired electron transport chain function, although the underlying mechanisms remain unclear. In this study, the impact of the CFTR modulators lumacaftor (VX-809) and ivacaftor (VX-770) on mitochondrial morphology and function was investigated in heterozygous \u0394F508\/W1282X CF IB3-1 cells. Combined treatment with VX-809 (10 \u03bcM, CFTR corrector) and VX-770 (0.1 \u03bcM, CFTR potentiator) induced a fragmented mitochondrial morphology in both CF and CF expressing wt-CFTR cells, without affecting cell viability or mitochondrial membrane potential (\u0394\u03a8m). While individual treatments differentially modulated ROS production and \u0394\u03a8m, these effects were not statistically significant under combined treatment. These results highlight a previously unrecognized role for CFTR modulators in shaping mitochondrial morphology. A better understanding of these effects may reveal novel mechanisms underlying the regulation of mitochondrial structure and function.<\/jats:p>","DOI":"10.3390\/cells14201601","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T11:57:42Z","timestamp":1760529462000},"page":"1601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Fragmentation Induced by the CFTR Modulators Lumacaftor and Ivacaftor in Immortalized Cystic Fibrosis Cell Lines"],"prefix":"10.3390","volume":"14","author":[{"given":"Camila","family":"Dib","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo A. Iglesias","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda de los \u00c1ngeles","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo L.","family":"Taminelli","sequence":"additional","affiliation":[{"name":"School of Engineering and Agrarian Sciences (FICA), Pontifical Catholic University of Argentina (UCA), Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Limpias del Valle","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia E.","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anal\u00eda G.","family":"Karadayian","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1s A.","family":"Santa-Coloma","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7928-4880","authenticated-orcid":false,"given":"\u00c1ngel G.","family":"Valdivieso","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), National Scientific and Technical Research Council of Argentina (CONICET), Alicia Moreau de Justo 1600, Buenos Aires 1107, Argentina"},{"name":"School of Engineering and Agrarian Sciences (FICA), Pontifical Catholic University of Argentina (UCA), Buenos Aires 1107, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1152\/physrev.1999.79.1.S23","article-title":"Structure and function of the CFTR chloride channel","volume":"79","author":"Sheppard","year":"1999","journal-title":"Physiol. 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