{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:11:53Z","timestamp":1790964713398,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Cystic Fibrosis Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Cystic Fibrosis (CF) is a genetic disease in which the intestine exhibits oxidative and inflammatory markers. As mitochondria are the central source and the main target of reactive oxygen species, we hypothesized that cystic fibrosis transmembrane conductance regulator (CFTR) defect leads to the disruption of cellular lipid homeostasis, which contributes to mitochondrial dysfunction. Methods. Mitochondrial functions and lipid metabolism were investigated in Caco-2\/15 cells with CFTR knockout (CFTR-\/-) engineered by the zinc finger nuclease technique. Experiments were performed under basal conditions and after the addition of the pro-oxidant iron-ascorbate (Fe\/Asc) complex. Results. Mitochondria of intestinal cells with CFTR-\/-, spontaneously showed an altered redox homeostasis characterised by a significant decrease in the expression of PPAR\u03b1 and nuclear factor like 2. Consistent with these observations, 8-oxoguanine-DNA glycosylase, responsible for repair of ROS-induced DNA lesion, was weakly expressed in CFTR-\/- cells. Moreover, disturbed fatty acid \u03b2-oxidation process was evidenced by the reduced expression of CPT1 and acyl-CoA dehydrogenase long-chain in CFTR-\/- cells. The decline of mitochondrial cytochrome c and B-cell lymphoma 2 expression pointing to magnified apoptosis. Mitochondrial respiration was also affected as demonstrated by the low expression of respiratory oxidative phosphorylation (OXPHOS) complexes and a high adenosine diphosphate\/adenosine triphosphate ratio. In contrast, the FAS and ACC enzymes were markedly increased, thereby indicating lipogenesis stimulation. This was associated with an augmented secretion of lipids, lipoproteins and apolipoproteins in CFTR-\/- cells. The addition of Fe\/Asc worsened while butylated hydroxy toluene partially improved these processes. Conclusions: CFTR silencing results in lipid homeostasis disruption and mitochondrial dysfunction in intestinal epithelial cells. Further investigation is needed to elucidate the mechanisms underlying the marked abnormalities in response to CFTR deletion.<\/jats:p>","DOI":"10.3390\/nu10070836","type":"journal-article","created":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T11:02:05Z","timestamp":1530097325000},"page":"836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["CFTR Deletion Confers Mitochondrial Dysfunction and Disrupts Lipid Homeostasis in Intestinal Epithelial Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Marie L.","family":"Kleme","sequence":"first","affiliation":[{"name":"Research Centre, CHU Sainte-Justine, 3175 Sainte-Catherine Rd., Montreal, QC H3T 1C5, Canada"},{"name":"Department of Nutrition, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, 2405 Sainte-Catherine Rd., Montreal, QC H3T 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"San\u00e9","sequence":"additional","affiliation":[{"name":"Research Centre, CHU Sainte-Justine, 3175 Sainte-Catherine Rd., Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Garofalo","sequence":"additional","affiliation":[{"name":"Research Centre, CHU Sainte-Justine, 3175 Sainte-Catherine Rd., Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-9791","authenticated-orcid":false,"given":"Ernest","family":"Seidman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Faculty of Medicine, IBD Laboratory, Research Institute, McGill University Health Center, McGill University, Montreal, QC H3G 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Brochiero","sequence":"additional","affiliation":[{"name":"Research Centre, CHU Sainte-Justine, 3175 Sainte-Catherine Rd., Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Berthiaume","sequence":"additional","affiliation":[{"name":"Montreal Clinical Research Institute, Montreal, QC H2W 1R7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Levy","sequence":"additional","affiliation":[{"name":"Research Centre, CHU Sainte-Justine, 3175 Sainte-Catherine Rd., Montreal, QC H3T 1C5, Canada"},{"name":"Department of Nutrition, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, 2405 Sainte-Catherine Rd., Montreal, QC H3T 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,27]]},"reference":[{"key":"ref_1","first-page":"26","article-title":"Epid\u00e9miologie et physiopathologie de la mucoviscidose","volume":"397","author":"Ravilly","year":"2007","journal-title":"Rev. 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