Dysfunction of mitochondria Ca2+ uptake in cystic fibrosis airway epithelial cells

Mitochondrion. 2009 Jul;9(4):232-41. doi: 10.1016/j.mito.2009.02.003. Epub 2009 Feb 26.


In the genetic disease cystic fibrosis (CF), the most common mutation F508del promotes the endoplasmic reticulum (ER) retention of misfolded CF proteins. Furthermore, in homozygous F508del-CFTR airway epithelial cells, the histamine Ca(2+) mobilization is abnormally increased. Because the uptake of Ca(2+) by mitochondria during Ca(2+) influx or Ca(2+) release from ER stores may be crucial for maintaining a normal Ca(2+) homeostasis, we compared the mitochondria morphology and distribution by transmission electron microscopy technique and the mitochondria membrane potential variation (DeltaPsi(mit)) using a fluorescent probe (TMRE) on human CF (CF-KM4) and non-CF (MM39) tracheal serous gland cell lines. Confocal imaging of Rhod-2-AM-loaded or of the mitochondrial targeted cameleon 4mtD3cpv-transfected human CF and non-CF cells, were used to examine the ability of mitochondria to sequester intracellular Ca(2+). The present study reveals that (i) the mitochondria network is fragmented in F508del-CFTR cells, (ii) the DeltaPsi(mit) of CF mitochondria is depolarized compared non-CF mitochondria, and (iii) the CF mitochondria Ca(2+) uptake is reduced compared non-CF cells. We propose that these defects in airway epithelial F508del-CFTR cells are the consequence of mitochondrial membrane depolarization leading to a deficient mitochondrial Ca(2+) uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cell Line
  • Cystic Fibrosis / pathology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology*
  • Epithelial Cells / ultrastructure
  • Humans
  • Membrane Potential, Mitochondrial*
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Mitochondria / ultrastructure
  • Respiratory System / pathology*


  • Calcium