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  The permeability transition pore signals apoptosis by directing Bax translocation and multimerization

De Giorgi, F., Lartigue, L., Bauer, M. K. A., Schubert, A., Grimm, S., Hanson, G. T., et al. (2002). The permeability transition pore signals apoptosis by directing Bax translocation and multimerization. FASEB Journal, 16(2), U153-U172.

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Genre: Journal Article
Alternative Title : Faseb J.

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 Creators:
De Giorgi, F., Author
Lartigue, L., Author
Bauer, M. K. A.1, Author              
Schubert, A.1, Author              
Grimm, S.2, Author              
Hanson, G. T., Author
Remington, S. J., Author
Youle, R. J., Author
Ichas, F., Author
Affiliations:
1External Organizations, ou_persistent22              
2Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              

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Free keywords: apoptosis; bax; cytochrome c; FRET; permeability transition pore
 Abstract: Mitochondria are key players of apoptosis and can irreversibly commit the cell to death by releasing cytochrome c (Cyt.c) to the cytosol, where caspases 9 and 3 subsequently get activated. Under conditions of oxidative stress, opening of the mitochondrial permeability transition pore (PTP) represents an early trigger and is crucial in causing Cyt.c release. To account for the latter, current models propose that PTP gating would result, as is the case in vitro, in the rupture of the outer mitochondrial membrane caused by mitochondrial matrix swelling. Using live cell imaging and recombinant fluorescent probes based on the green fluorescent protein (GFP) and its mutants, we report that directed repetitive gating of the PTP triggers a delayed Cyt.c efflux, which is not associated with mitochondrial swelling. Instead, subcellular imaging shows that PTP opening signals the redistribution of the cytosolic protein Bax to the mitochondria, where it secondarily forms clusters that appear to be a prerequisite for Cyt.c release. Fluorescence resonance energy transfer imaging further reveals that Bax clustering coincides with the formation of Bax multimers. We conclude that the PTP is not itself a component of the Cyt.c release machinery, but that it acts indirectly by signaling Bax translocation and multimerization.

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Language(s): eng - English
 Dates: 2002-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 39139
ISI: 000174203700007
 Degree: -

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Title: FASEB Journal
  Alternative Title : Faseb J.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 16 (2) Sequence Number: - Start / End Page: U153 - U172 Identifier: ISSN: 0892-6638