CISD1 codifies a mitochondrial protein upregulated by the CFTR channel

What is it about?

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.

Featured Image

Why is it important?

We showed that CISD1 is mostly located to mitochondria, although in dividing cells it could be present also in nucleus. Many functions has been attributed to this protein since we cloned it several years ago. All are so different that we are not really sure of its actual function yet.

Perspectives