Voltage-dependent anion channel involved in the mitochondrial calcium cycle of cell lines carrying the mitochondrial DNA A4263G mutation

• Published in: Biochemical and biophysical research communications 2011-01, Vol.404 (1), p.364-369
• Main Authors: Liu, Yuqi, Gao, Lei, Xue, Qiao, Li, Zongbin, Wang, Lin, Chen, Rui, Liu, Mohan, Wen, Yi, Guan, Minxin, Li, Yang, Wang, Shiwen
• Format: Article
• Language: English
• Subjects: adenine nucleotides; Asian Continental Ancestry Group - genetics; calcium; Calcium - metabolism; Cell Line; DNA, Mitochondrial - genetics; fluorescence; Humans; Hypertension - genetics; Hypertension - metabolism; ion channels; membrane permeability; membrane potential; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial calcium cycle; mitochondrial DNA; Mitochondrial DNA (mtDNA); mitochondrial membrane; Mitochondrial membrane potential; Mutation; Pedigree; VDAC; Voltage-Dependent Anion Channels - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2010.11.124

► We first reported a Chinese family carrying tRNAIle A4263G mutation associated with hypertension. We did further investigations on the mechanism of mtDNA mutation contributing to hypertension. ► We found the mitochondrial Ca2+ concentration and membrane potential (ΔΨm) of the cell lines carrying this mutation was lower than that of the control group. ► The difference between mutated cell lines and control cells was diminished by Cyclosporin A (VDAC blocker). So VDAC is involved in the increase of mitochondrial permeability to Ca2+ and decrease of mitochondrial membrane potential of the cell lines carrying this mutations. 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 tRNAIle A4263G mutation were lower than those of the control group (P