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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Main Authors: Mohan Liu, Rui Chen, Lin Wang, Hua Xu, Zongbin Li, Yang Li, Lei Gao, Yuqi Liu, Yi Wen, Minxin Guan, Shiwen Wang
Format: Article
Language:English
Published: BMC 2009-11-01
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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