Effect of voltage-dependent anion channel on apoptosis of cell lines carrying mitochondrial DNA A4263G mutation

AIM: To study the effect of voltage-dependent anion channel (VDAC) on apoptosis of cell lines carrying mitochondrial DNA A4263G mutation. METHODS: We established lymphoblastoid cell lines from three symptomatic and one asymptomatic individual in a family carrying A4263G mutation and we compared this with three control cell lines. Mitochondrial potential was detected by flow cytometry, and the combination of VDAC and Bax was evaluated by confocal images. RESULTS: Expression of VDAC and Bax in individuals carrying mtDNA A4263G mutation increased compared with those in the control group, whereas no changes were found in the expression of small conductance calcium-dependant potassium (sKCa). Flow cytometry showed that mitochondrial potential (ΔΨm) of individuals carrying mtDNA A4263G mutation decreased 32% compared with the control group (P<0.05) and this difference was attenuated by cyclosporin A (CsA), a blocker of VDAC. Confocal images showed that VDAC was associated with Bax in individuals carrying mtDNA A4263G mutation, whereas the combination was not seen in the control group. CONCLUSION: Abnormality of mitochondrial VDAC leads to the significant increase of apoptosis of cell lines carrying mtDNA A4263G mutations.