CFTR Chloride Channel Modulates the Mitochondrial Dynamics

CLAUZURE, MARIÁNGELES; AGUILAR, MARÍA DE LOS A.; VARELA, ROCÍO; MORI, CONSUELO; VALDIVIESO, ANGEL G.; MASSIP-COPIZ, MARÍA M; SANTA-COLOMA, TOMÁS A.

CABA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS. LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica - SAIC.; 2017

Cystic Fibrosis (CF) is caused by mutations in the gene CFTR, encoding a cAMP-activated chloride (Cl-) channel. Previously, we have reported that the impairment of the CFTR channel activity leads to a variety of alterations, including differential gene expression and mitochondrial dysfunction. We found a reduced expression of the genes MTND4 (mitochondrial gene) and CISD1 (nuclear gene) in CF models that was later associated to a reduced mitochondrial complex-I activity (mCx-I). The aim of this work was investigating if the CFTR activity was involved in the mitochondrial dynamics regulation. The mitochondrial network morphology was studied in the CF cell line IB3-1 and compared with S9 or C38 cells that are IB3-1 cells with the CFTR activity restored. Mitochondria of these cells were labelled by the mitochondrial probe TMRM or transfecting plasmids pMito-YFP and pMito-Cherry. Mitochondria morphology was analyzed in cells with basal or AMPc stimulated for 24 h in serum-free medium by confocal microscopy. An increased (p < 0.05) small mitochondria population was observed in CF cells compared to control cells. The CFTR activity role in mitochondrial dynamics was then tested in C38 cells expressing pMito-YFP treated with two specific CFTR inhibitors (GlyH101 and CFTR(inh)-172) and analyzed by time series confocal microscopy in live-cells. The treatment with CFTR inhibitors showed an early (30 seconds) mitochondrial fragmentation induction (p