title: The mitochondrial complex I activity is reduced in cells with impaired cystic fibrosis transmembrane conductance regulator (CFTR) function.
abstract: Cystic fibrosis (CF) is a frequent and lethal autosomal recessive disease. It results from different possible mutations in the CFTR gene, which encodes the CFTR chloride channel. We have previously studied the differential expression of genes in CF and CF corrected cell lines, and found a reduced expression of MTND4 in CF cells. MTND4 is a mitochondrial gene encoding the MTND4 subunit of the mitochondrial Complex I (mCx-I). Since this subunit is essential for the assembly and activity of mCx-I, we have now studied whether the activity of this complex was also affected in CF cells. By using Blue Native-PAGE, the in-gel activity (IGA) of the mCx-I was found reduced in CFDE and IB3-1 cells (CF cell lines) compared with CFDE/6RepCFTR and S9 cells, respectively (CFDE and IB3-1 cells ectopically expressing wild-type CFTR). Moreover, colon carcinoma T84 and Caco-2 cells, which express wt-CFTR, either treated with CFTR inhibitors (glibenclamide, CFTR(inh)-172 or GlyH101) or transfected with a CFTR-specific shRNAi, showed a significant reduction on the IGA of mCx-I. The reduction of the mCx-I activity caused by CFTR inhibition under physiological or pathological conditions may have a profound impact on mitochondrial functions of CF and non-CF cells.
authors.affiliation: Institute for Biomedical Research, Laboratory of Cellular and Molecular Biology, School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina.
authors.forename: Angel G
authors.initials: AG
authors.lastname: Valdivieso
authors.forename: Mariángeles
authors.initials: M
authors.lastname: Clauzure
authors.forename: María C
authors.initials: MC
authors.lastname: Marín
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Taminelli
authors.forename: María M
authors.initials: MM
authors.lastname: Massip Copiz
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez
authors.forename: Gustavo
authors.initials: G
authors.lastname: Schulman
authors.forename: María L
authors.initials: ML
authors.lastname: Teiber
authors.forename: Tomás A
authors.initials: TA
authors.lastname: Santa-Coloma
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D003550:Cystic Fibrosis / Q000201:enzymology* / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009245:NADH Dehydrogenase / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: C098483:NADH dehydrogenase subunit 4; D034741:RNA, Small Interfering; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I