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PMID: 12193163 Published · ppublish English Journal Article

Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein.

The Biochemical journal ·Vol. 368 ·No. Pt 3 ·2002-12-15 ·Pages 915-21

Roucou X, Montessuit S, Antonsson B, Martinou JC

Abstract

In response to various apoptotic stimuli, Bax, a pro-apoptotic member of the Bcl-2 family, is oligomerized and permeabilizes the mitochondrial outer membrane to apoptogenic factors, including cytochrome c. Bax oligomerization can also be induced by incubating isolated mitochondria containing endogenous Bax with recombinant tBid (caspase-8-cleaved Bid) in vitro. The mechanism by which Bax oligomerizes under these conditions is still unknown. To address this question, recombinant human full-length Bax was purified as a monomeric protein. Bax failed to oligomerize spontaneously in isolated mitochondria or in liposomes composed of either cardiolipin or lipids extracted from mitochondria. However, in the presence of tBid, the protein formed large complexes in mitochondrial membranes and induced the release of cytochrome c. tBid also induced Bax oligomerization in isolated mitochondrial outer membranes, but not in other membranes, such as plasma membranes or microsomes. Moreover, tBid-induced Bax oligomerization was inhibited when mitochondria were pretreated with protease K. The presence of the voltage-dependent anion channel was not required either for Bax oligomerization or for Bax-induced cytochrome c release. Finally, Bax oligomerization was reconstituted in proteoliposomes made from mitochondrial membrane proteins. These findings imply that tBid is necessary but not sufficient for Bax oligomerization; a mitochondrial protein is also required.

MeSH Terms
Animals Apoptosis BH3 Interacting Domain Death Agonist Protein Carrier Proteins/metabolism Cell Membrane/metabolism Chromatography, Gel Cytochrome c Group/metabolism Dose-Response Relationship, Drug Endopeptidase K/metabolism,pharmacology HeLa Cells Histidine/metabolism Humans Intracellular Membranes/metabolism Liposomes/metabolism Mice Microsomes/metabolism Microsomes, Liver/metabolism Mitochondria/metabolism Protein Structure, Tertiary Proteolipids/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-bcl-2 Rats bcl-2-Associated X Protein
Chemicals
BAX protein, human BH3 Interacting Domain Death Agonist Protein BID protein, human Bax protein, mouse Bax protein, rat Bid protein, mouse Bid protein, rat Carrier Proteins Cytochrome c Group Liposomes Proteolipids Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 bcl-2-Associated X Protein proteoliposomes Histidine Endopeptidase K
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Roucou Xavier
Departement de Biologie Cellulaire, University of Geneva, 30 quai E. Ansermet, 1211 Geneva 4, Switzerland.
Montessuit Sylvie
Antonsson Bruno
Martinou Jean-Claude
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/BJ20020972
Published
2002-12-15
Pages
915-21
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1223025
Subset
IM
External Links
PubMed source DOI: 10.1042/BJ20020972 PMC Full Text View journal details
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