Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis.
The proapoptotic Bax protein induces cell death by acting on mitochondria. Bax binds to the permeability transition pore complex (PTPC), a composite proteaceous channel that is involved in the regulation of mitochondrial membrane permeability. Immunodepletion of Bax from PTPC or purification of PTPC from Bax-deficient mice yielded a PTPC that could not permeabilize membranes in response to atractyloside, a proapoptotic ligand of the adenine nucleotide translocator (ANT). Bax and ANT coimmunoprecipitated and interacted in the yeast two-hybrid system. Ectopic expression of Bax induced cell death in wild-type but not in ANT-deficient yeast. Recombinant Bax and purified ANT, but neither of them alone, efficiently formed atractyloside-responsive channels in artificial membranes. Hence, the proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.
Marzo
I
I
CNRS, UPR 420, 19 rue Guy Môquet, F-94801 Villejuif, France.
Brenner
C
C
Zamzami
N
N
Jürgensmeier
J M
JM
Susin
S A
SA
Vieira
H L
HL
Prévost
M C
MC
Xie
Z
Z
Matsuyama
S
S
Reed
J C
JC
Kroemer
G
G
D000818:Animals; D017209:Apoptosis; D001278:Atractyloside / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D001865:Bongkrekic Acid / Q000378:metabolism / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D019281:Dimerization; D019073:HT29 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics; D014162:Transfection; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C494828:Bax protein, rat; D008081:Liposomes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D001865:Bongkrekic Acid; D001278:Atractyloside; D016572:Cyclosporine; D000226:Mitochondrial ADP, ATP Translocases