MODULATION OF CISD1 EXPRESSION BY THE ACTIVITY OF THE CFTR CHANNEL

MARIÁNGELES CLAUZURE; TOMÁS A. SANTA COLOMA; CONSUELO MORI; ANGEL GABRIEL VALDIVIESO; MARÍA MACARENA MASSIP COPIZ

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Cystic fibrosis (CF) is a frequent autosomal recessive disease caused by mutations that impair the CF transmembrane conductance regulator (CFTR) protein function, which indirectly affect the expression of a net of genes. We described a new CFTR-dependent gene downregulated in CF cells, CISD1, also referred to as mitoNEET, encoding for the first member of a family of proteins possessing a CDGSH signature. CISD1 is a dimeric mitochondrial outer membrane protein, implicated in many facets of human pathophysiology, but its molecular function remains poorly characterized. We have previously described that CISD1 gene expression was decreased in a CF cellular model and restored in the same cells ectopically expressing wt-CFTR (CFDE and CFDE/6RepCFTR cells). Now we used another cellular model, human colon adenocarcinoma T84 cells, and by real-time PCR we determined that CISD1 gene expression was decreased in T84 cells treated with CFTR(inh)172, compared to control cells (p2.5 ng/ml) inhibit CFTR mRNA expression in T84 cells. Here we show that externally added IL-1β (5 ng/ml) reduces the CISD1 mRNA expression. Moreover, treatments with IKK inhibitor II (NF-κB pathway) increased the CISD1 mRNA expression. In conclusion, CISD1 gene expression is decreased in cells with impaired CFTR function. Similar effects were obtained when exogenous IL-1β was added. These results suggest that IL-1β acts as a bridge connecting the CFTR with the CISD1 expression. Acknowledgments: ANPCYT (grant numbers PICT 2012-1278 and PICT-2015-1031), CONICET (grant PIP 11220150100227CO 2015-2017 and PUE 22920160100129CO) and UCA; also by research fellowships from CONICET.