Research article

Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation

Liu Yuqi^1* , Gao Lei^1* , Li Yang^1* , Li Zongbin¹ , Xu Hua² , Wang Lin¹ , Chen Rui¹ , Liu Mohan¹ , Wen Yi¹ , Guan Minxin³ and Wang Shiwen¹

¹  Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, 100853, PR China

²  Military Medical Science Academy of the Chinese PLA, Beijing, 100850, PR China

³  Cincinnati Children's Hospital Medical Center, Division of Human Genetics, Cincinnati, OH 45229, USA

author email corresponding author email* Contributed equally

BMC Medical Genetics 2009, 10:114doi:10.1186/1471-2350-10-114

Published:	9 November 2009

Abstract

Background

The mitochondrial voltage-dependent anion channel (VDAC) is increasingly implicated in the control of apoptosis. We have studied the effects the mitochondrial DNA (mtDNA) tRNA^Ile mutation on VDAC expression, localization, and apoptosis.

Methods

Lymphoblastoid cell lines were derived from 3 symptomatic and 1 asymptomatic members of a family with hypertension associated with the A4263G tRNA^Ile mutation as well as from control subjects. Mitochondrial potential (ΔΨ_m) and apoptosis were measured by flow cytometry; co-localization of VDAC and Bax was evaluated by confocal microscopy.

Results

Expression of VDAC and Bax in mtDNA cell lines was found to be increased compared to controls, while expression of the small conductance calcium-dependant potassium channel (sK_Ca) was unchanged. Confocal imaging revealed co-localization of VDAC/Bax on the outer mitochondrial membrane of A4263G cell lines but not from controls. Flow cytometry indicated that the mitochondrial potential was decreased by 32% in mutated cells versus controls while rates of apoptosis were increased (P < 0.05). The difference was attenuated by Cyclosporin A (CsA, 2 μM), a blocker of VDAC.

Conclusion

We conclude that increased expression of mitochondrial VDAC and subcellular co-localization of VDAC/Bax increases mitochondrial permeability and apoptosis in cell lines carrying the mtDNA tRNA^Ile A4263G mutation.