title: The mitochondrial TOM complex is required for tBid/Bax-induced cytochrome c release.
abstract: Cytochrome c release from mitochondria is a key event in apoptosis signaling that is regulated by Bcl-2 family proteins. Cleavage of the BH3-only protein Bid by multiple proteases leads to the formation of truncated Bid (tBid), which, in turn, promotes the oligomerization/insertion of Bax into the mitochondrial outer membrane and the resultant release of proteins residing in the intermembrane space. Bax, a monomeric protein in the cytosol, is targeted by a yet unknown mechanism to the mitochondria. Several hypotheses have been put forward to explain this targeting specificity. Using mitochondria isolated from different mutants of the yeast Saccharomyces cerevisiae and recombinant proteins, we have now investigated components of the mitochondrial outer membrane that might be required for tBid/Bax-induced cytochrome c release. Here, we show that the protein translocase of the outer mitochondrial membrane is required for Bax insertion and cytochrome c release.
authors.affiliation: Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ott
authors.forename: Erik
authors.initials: E
authors.lastname: Norberg
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Walter
authors.forename: Patrick
authors.initials: P
authors.lastname: Schreiner
authors.forename: Christian
authors.initials: C
authors.lastname: Kemper
authors.forename: Doron
authors.initials: D
authors.lastname: Rapaport
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: Sten
authors.initials: S
authors.lastname: Orrenius
mesh_terms: D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D019286:Endopeptidase K / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D008954:Models, Biological; D009492:Neurospora crassa / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D019286:Endopeptidase K