Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation.
BMC Med Genet
; 10: 114, 2009 Nov 09.
Article
em En
| MEDLINE
| ID: mdl-19895710
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
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Apoptose
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Proteína X Associada a bcl-2
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Canais de Ânion Dependentes de Voltagem
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Hipertensão
Limite:
Female
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Humans
/
Male
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article