title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yuqi
authors.forename: Gao
authors.initials: G
authors.lastname: Lei
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Zongbin
authors.forename: Xu
authors.initials: X
authors.lastname: Hua
authors.forename: Wang
authors.initials: W
authors.lastname: Lin
authors.forename: Chen
authors.initials: C
authors.lastname: Rui
authors.forename: Liu
authors.initials: L
authors.lastname: Mohan
authors.forename: Wen
authors.initials: W
authors.lastname: Yi
authors.forename: Guan
authors.initials: G
authors.lastname: Minxin
authors.forename: Wang
authors.initials: W
authors.lastname: Shiwen
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002461:Cell Line, Transformed; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008214:Lymphocytes; D008297:Male; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D009154:Mutation; D010375:Pedigree; D050994:Voltage-Dependent Anion Channels / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494826:BAX protein, human; D004272:DNA, Mitochondrial; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein