CISD1 codifies a mitochondrial protein upregulated by the CFTR channel.
Cystic fibrosis (CF) is an autosomic recessive disease caused by mutations in the CFTR chloride channel, which indirectly affect the expression of a net of genes. Here we describe a new CFTR-dependent gene, CISD1, encoding for the first member of a family of proteins possessing a CDGSH signature. CISD1 mRNA is down-regulated in cystic fibrosis cells, and restored in the same cells ectopically expressing wt-CFTR (CFDE and CFDE/6RepCFTR; IB3-1 and S9 cells). Inhibition of CFTR chloride transport activity by using glibenclamide (50muM, 24h) or CFTR(inh)-172 (5muM, 24h), resulted in the down-regulation of CISD1 mRNA, and CFTR stimulation with cAMP/isoproterenol/IBMX upregulated its expression. As predicted by PSORT II, a CISD1-GFP chimera was found to be located into mitochondria, suggesting a possible role in the function/regulation of mitochondrial activity, in agreement with earlier observations of a possible mitochondrial failure in cystic fibrosis.
Taminelli
Guillermo L
GL
Laboratorio de Biología Celular y Molecular, Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Sotomayor
Verónica
V
Valdivieso
Angel G
AG
Teiber
María L
ML
Marín
María C
MC
Santa-Coloma
Tomás A
TA
D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D015854:Up-Regulation
C525595:CISD1 protein, human; D024101:Mitochondrial Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator