Publication Date:
1998-09-25
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marzo, I -- Brenner, C -- Zamzami, N -- Jurgensmeier, J M -- Susin, S A -- Vieira, H L -- Prevost, M C -- Xie, Z -- Matsuyama, S -- Reed, J C -- Kroemer, G -- New York, N.Y. -- Science. 1998 Sep 25;281(5385):2027-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, UPR 420, 19 rue Guy Moquet, F-94801 Villejuif, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9748162" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Atractyloside/metabolism/pharmacology
;
Binding Sites
;
Bongkrekic Acid/metabolism/pharmacology
;
Cyclosporine/pharmacology
;
Dimerization
;
HT29 Cells
;
Humans
;
Intracellular Membranes/physiology
;
Liposomes
;
Mice
;
Mice, Inbred C57BL
;
Mitochondria/*physiology
;
Mitochondrial ADP, ATP Translocases/chemistry/*metabolism
;
Permeability
;
Proto-Oncogene Proteins/chemistry/genetics/*metabolism/pharmacology
;
Proto-Oncogene Proteins c-bcl-2/pharmacology
;
Rats
;
Rats, Wistar
;
Recombinant Proteins/pharmacology
;
Saccharomyces cerevisiae/cytology/genetics
;
Transfection
;
bcl-2-Associated X Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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