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

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) tRNAIle 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 tRNAIle mutation as well as from control subjects. Mitochondrial potential (DeltaPsim) 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 (sKCa) 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 muM), 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 tRNAIle A4263G mutation.

• Authors: Liu Yuqi, Gao Lei, Li Yang, Li Zongbin, Xu Hua, Wang Lin, Chen Rui, Liu Mohan, Wen Yi, Guan Minxin, Wang Shiwen
• Journal: BMC medical genetics (BMC Med Genet) Vol. 10 Pg. 114 (Nov 09 2009) ISSN: 1471-2350 [Electronic] England
• PMID: 19895710 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• DNA, Mitochondrial
• Voltage-Dependent Anion Channels
• bcl-2-Associated X Protein

Topics

• Apoptosis (genetics)
• Cell Line, Transformed
• DNA, Mitochondrial (genetics)
• Female
• Gene Expression
• Humans
• Hypertension (genetics, physiopathology)
• Lymphocytes
• Male
• Membrane Potentials
• Microscopy, Confocal
• Mutation
• Pedigree
• Voltage-Dependent Anion Channels (genetics)
• bcl-2-Associated X Protein (genetics)