期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 404, 期 1, 页码 364-369出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.11.124
关键词
Mitochondrial DNA (mtDNA); VDAC; Mitochondrial calcium cycle; Mitochondrial membrane potential
资金
- National Key Basic Research and Development Project 973 Fund [2007CB07403]
In this study, we investigated the effects of the voltage-dependent anion channel (VDAC) on the mitochondrial calcium cycle in cell lines carrying the mitochondrial DNA A4263G mutation. We established lymphoblastoid cell lines from three symptomatic individuals and one asymptomatic individual from the large Chinese Han family carrying the A4263G mutation; these were compared with three control cell lines. The mitochondrial Ca2+ concentration and membrane potential were detected by loading cells with Rhod-2 and JC-1, respectively. Confocal imagines showed the average Rhod-2 and JC-1 fluorescence levels of individuals carrying the tRNA(Ile) A4263G mutation were lower than those of the control group (P < 0.05). The baseline Rhod-2 fluorescence in the control group increased after exposure to atractyloside (an opener of the adenine nucleotide translocator, P < 0.05), but no significant change was detected in the cell line harboring the A4263G mutation (P > 0.05). The baseline JC-1 fluorescence in both the mutated and control cell lines decreased after subsequent exposure to atractyloside (P < 0.05), whereas this effect of atractyloside was inhibited by Cyclosporin A (CsA, a VDAC blocker). We conclude that the mitochondrial VDAC is involved in both the increase of mitochondrial permeability to Ca2+ and the decrease of mitochondrial membrane potential in cell lines carrying the mtDNA A4263G mutation. (C) 2010 Elsevier Inc. All rights reserved.
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