期刊
MITOCHONDRION
卷 9, 期 4, 页码 232-241出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2009.02.003
关键词
Ca2+ signalling; F508del-CFTR; Pharmacology; Mitochondria; Cystic fibrosis
资金
- Vaincre la Mucoviscidose (VLM)
- CNRS
- Swiss National Foundation [320000-107622]
- Foundation Carlos and Elsie de Reuter Fabrice Antigny
In the genetic disease cystic fibrosis (CF), the most common mutation F508del promotes the endoplasmic reticulum (ER) retention of misfolded CIF proteins. Furthermore, in homozygous F508del-CFTR airway epithelial cells, the histamine Ca2+ mobilization is abnormally increased. Because the uptake of Ca2+ by mitochondria during Ca2+ influx or Ca2+ release from ER stores may be crucial for maintaining a normal Ca2+ homeostasis, we compared the mitochondria morphology and distribution by transmission electron microscopy technique and the mitochondria membrane potential variation (Delta Psi(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 Ca2+. The present study reveals that (i) the mitochondria network is fragmented in F508del-CFTR cells, (ii) the Delta Psi(mit) of CF mitochondria is depolarized compared to non-CF mitochondria, and (iii) the CF mitochondria Ca2+ uptake is reduced compared to 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 Ca2+ uptake. (C) 2009 Elsevier B.V. on behalf of Mitochondria Research Society. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据