Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis

I Marzo, C Brenner, N Zamzami, JM Jürgensmeier… - Science, 1998 - science.org
I Marzo, C Brenner, N Zamzami, JM Jürgensmeier, SA Susin, HLA Vieira, MC Prévost…
Science, 1998science.org
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 …
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.
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