title: Dysfunction of mitochondria Ca2+ uptake in cystic fibrosis airway epithelial cells.
abstract: 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.
authors.affiliation: Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, CNRS, 40 Avenue du recteur pineau, Poitiers F-86022, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Antigny
authors.forename: Nathalie
authors.initials: N
authors.lastname: Girardin
authors.forename: Dorothée
authors.initials: D
authors.lastname: Raveau
authors.forename: Maud
authors.initials: M
authors.lastname: Frieden
authors.forename: Frédéric
authors.initials: F
authors.lastname: Becq
authors.forename: Clarisse
authors.initials: C
authors.lastname: Vandebrouck
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D012137:Respiratory System / Q000473:pathology*
chemical_list: D002118:Calcium