The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91339
Title:
The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol.
Authors:
Kluck, Ruth M; Esposti, Mauro Dogli; Perkins, Guy; Renken, Christian; Kuwana, Tomomi; Bossy-Wetzel, Ella; Goldberg, Martin W; Allen, Terence D; Barber, Michael J; Green, Douglas R; Newmeyer, Donald D
Abstract:
During apoptosis, an important pathway leading to caspase activation involves the release of cytochrome c from the intermembrane space of mitochondria. Using a cell-free system based on Xenopus egg extracts, we examined changes in the outer mitochondrial membrane accompanying cytochrome c efflux. The pro-apoptotic proteins, Bid and Bax, as well as factors present in Xenopus egg cytosol, each induced cytochrome c release when incubated with isolated mitochondria. These factors caused a permeabilization of the outer membrane that allowed the corelease of multiple intermembrane space proteins: cytochrome c, adenylate kinase and sulfite oxidase. The efflux process is thus nonspecific. None of the cytochrome c-releasing factors caused detectable mitochondrial swelling, arguing that matrix swelling is not required for outer membrane permeability in this system. Bid and Bax caused complete release of cytochrome c but only a limited permeabilization of the outer membrane, as measured by the accessibility of inner membrane-associated respiratory complexes III and IV to exogenously added cytochrome c. However, outer membrane permeability was strikingly increased by a macromolecular cytosolic factor, termed PEF (permeability enhancing factor). We hypothesize that PEF activity could help determine whether cells can recover from mitochondrial cytochrome c release.
Affiliation:
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Citation:
The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol. 1999, 147 (4):809-22 J. Cell Biol.
Journal:
Journal of Cell Biology
Issue Date:
15-Nov-1999
URI:
http://hdl.handle.net/10541/91339
PubMed ID:
10562282
Type:
Article
Language:
en
ISSN:
0021-9525
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKluck, Ruth Men
dc.contributor.authorEsposti, Mauro Doglien
dc.contributor.authorPerkins, Guyen
dc.contributor.authorRenken, Christianen
dc.contributor.authorKuwana, Tomomien
dc.contributor.authorBossy-Wetzel, Ellaen
dc.contributor.authorGoldberg, Martin Wen
dc.contributor.authorAllen, Terence Den
dc.contributor.authorBarber, Michael Jen
dc.contributor.authorGreen, Douglas Ren
dc.contributor.authorNewmeyer, Donald Den
dc.date.accessioned2010-02-08T11:04:31Z-
dc.date.available2010-02-08T11:04:31Z-
dc.date.issued1999-11-15-
dc.identifier.citationThe pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol. 1999, 147 (4):809-22 J. Cell Biol.en
dc.identifier.issn0021-9525-
dc.identifier.pmid10562282-
dc.identifier.urihttp://hdl.handle.net/10541/91339-
dc.description.abstractDuring apoptosis, an important pathway leading to caspase activation involves the release of cytochrome c from the intermembrane space of mitochondria. Using a cell-free system based on Xenopus egg extracts, we examined changes in the outer mitochondrial membrane accompanying cytochrome c efflux. The pro-apoptotic proteins, Bid and Bax, as well as factors present in Xenopus egg cytosol, each induced cytochrome c release when incubated with isolated mitochondria. These factors caused a permeabilization of the outer membrane that allowed the corelease of multiple intermembrane space proteins: cytochrome c, adenylate kinase and sulfite oxidase. The efflux process is thus nonspecific. None of the cytochrome c-releasing factors caused detectable mitochondrial swelling, arguing that matrix swelling is not required for outer membrane permeability in this system. Bid and Bax caused complete release of cytochrome c but only a limited permeabilization of the outer membrane, as measured by the accessibility of inner membrane-associated respiratory complexes III and IV to exogenously added cytochrome c. However, outer membrane permeability was strikingly increased by a macromolecular cytosolic factor, termed PEF (permeability enhancing factor). We hypothesize that PEF activity could help determine whether cells can recover from mitochondrial cytochrome c release.en
dc.language.isoenen
dc.subject.meshAdenylate Kinase-
dc.subject.meshAlamethicin-
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshBH3 Interacting Domain Death Agonist Protein-
dc.subject.meshCarrier Proteins-
dc.subject.meshCell-Free System-
dc.subject.meshCytochrome c Group-
dc.subject.meshCytosol-
dc.subject.meshElectron Transport Complex III-
dc.subject.meshElectron Transport Complex IV-
dc.subject.meshIntracellular Membranes-
dc.subject.meshKinetics-
dc.subject.meshMale-
dc.subject.meshMicroscopy, Electron-
dc.subject.meshMicroscopy, Electron, Scanning-
dc.subject.meshMitochondria, Liver-
dc.subject.meshOocytes-
dc.subject.meshPeptide Hydrolases-
dc.subject.meshPermeability-
dc.subject.meshProto-Oncogene Proteins-
dc.subject.meshProto-Oncogene Proteins c-bcl-2-
dc.subject.meshRats-
dc.subject.meshRats, Sprague-Dawley-
dc.subject.meshRecombinant Proteins-
dc.subject.meshXenopus laevis-
dc.subject.meshbcl-2-Associated X Protein-
dc.titleThe pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol.en
dc.typeArticleen
dc.contributor.departmentDivision of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.en
dc.identifier.journalJournal of Cell Biologyen
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