Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation
<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<sup>Ile </sup>mutation on VDAC expression, lo...
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BMC
2009-11-01
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Series: | BMC Medical Genetics |
Online Access: | http://www.biomedcentral.com/1471-2350/10/114 |
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author | Mohan Liu Rui Chen Lin Wang Hua Xu Zongbin Li Yang Li Lei Gao Yuqi Liu Yi Wen Minxin Guan Shiwen Wang |
author_facet | Mohan Liu Rui Chen Lin Wang Hua Xu Zongbin Li Yang Li Lei Gao Yuqi Liu Yi Wen Minxin Guan Shiwen Wang |
author_sort | Mohan Liu |
collection | DOAJ |
description | <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<sup>Ile </sup>mutation 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<sup>Ile </sup>mutation as well as from control subjects. Mitochondrial potential (ΔΨ<sub>m</sub>) 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<sub>Ca</sub>) 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<sup>Ile </sup>A4263G mutation.</p> |
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spelling | doaj.art-5c63519cba2941f598ae82d4e2a14ab12022-12-22T04:11:31ZengBMCBMC Medical Genetics1471-23502009-11-0110111410.1186/1471-2350-10-114Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutationMohan LiuRui ChenLin WangHua XuZongbin LiYang LiLei GaoYuqi LiuYi WenMinxin GuanShiwen Wang<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<sup>Ile </sup>mutation 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<sup>Ile </sup>mutation as well as from control subjects. Mitochondrial potential (ΔΨ<sub>m</sub>) 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<sub>Ca</sub>) 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<sup>Ile </sup>A4263G mutation.</p>http://www.biomedcentral.com/1471-2350/10/114 |
spellingShingle | Mohan Liu Rui Chen Lin Wang Hua Xu Zongbin Li Yang Li Lei Gao Yuqi Liu Yi Wen Minxin Guan Shiwen Wang Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation BMC Medical Genetics |
title | Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation |
title_full | Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation |
title_fullStr | Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation |
title_full_unstemmed | Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation |
title_short | Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation |
title_sort | voltage dependent anion channel vdac is involved in apoptosis of cell lines carrying the mitochondrial dna mutation |
url | http://www.biomedcentral.com/1471-2350/10/114 |
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