ZCD1 IS A NEW MITOCONDRIAL-LOCATED PROTEIN DOWN-REGULATED IN CYSTIC FIBROSIS

TAMINELLI GL; VALDIVIESO AG; TEIBER ML; DANKERT MA; SANTA COLOMA TA

Rosario, Argentina

Congreso; Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB), XLII Reunión Anual.; 2006

SAIB

We have characterized a CFTR-dependent gene, ZCD1, which codifies for the first member of a new Zn-finger family. The function is unknown yet. ZCD1 mRNA is negatively modulated in CFDE cells (Cystic Fibrosis, CF) and its levels are recovered in CFDE cells ectopically expressing wt CFTR. Confocal FISH, in situ hybridization, and semi-quantitative RT-PCRs confirmed these results. Cells treatment with glibenclamide (50 mM, 24 h), produced a reduction in the ZCD1 mRNA levels. The protein sequence of ZCD1 has a motive for mitochondrial translocation, as predicted by using PSORT II. Transfecting CFDE cells with a chimera of ZCD1 and EGFP, and comparing the results with cells treated with TMRM (a mitochondrial specific dye), we have observed by confocal microscopy that the mitochondrial prediction of its location was correct. At present, we are performing additional studies by using a more specific inhibitor than glibenclamide (CFTR(Inh)-172), recently developed by other researchers, and using CFTR and ZCD1 siRNAs to attempt to define its possible biological function, most likely related to the mitocondrial activity. Its downregulation in cystic fibrosis might explain mitochondrial failures reported many years ago in CF, for which the mechanisms are still unknown. Acknowledgements: University of Buenos Aires, CONICET, and ANPCyT.