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<p>Abstract</p> <p>Background</p> <p>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^Ilemutation on VDAC expression, localization, and apoptosis.</p> <p>Methods</p> <p>Lymphoblastoid cell lines were derived from 3 symptomatic and 1 asymptomatic members of a family with hypertension associated with the A4263G tRNA^Ilemutation 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.</p> <p>Results</p> <p>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 (<it>P </it>< 0.05). The difference was attenuated by Cyclosporin A (CsA, 2 μM), a blocker of VDAC.</p> <p>Conclusion</p> <p>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^IleA4263G mutation.</p>