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Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol

Edlich, F. and Banerjee, S. and Suzuki, M. and Cleland, M. M. and Arnoult, D. and Wang, C. and Neutzner, A. and Tjandra, N. and Youle, R. J.. (2011) Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell, Vol. 145, H. 1. pp. 104-116.

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Official URL: http://edoc.unibas.ch/dok/A6338227

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Abstract

The Bcl-2 family member Bax translocates from the cytosol to mitochondria, where it oligomerizes and permeabilizes the mitochondrial outer membrane to promote apoptosis. Bax activity is counteracted by prosurvival Bcl-2 proteins, but how they inhibit Bax remains controversial because they neither colocalize nor form stable complexes with Bax. We constrained Bax in its native cytosolic conformation within cells using intramolecular disulfide tethers. Bax tethers disrupt interaction with Bcl-x(L) in detergents and cell-free MOMP activity but unexpectedly induce Bax accumulation on mitochondria. Fluorescence loss in photobleaching (FLIP) reveals constant retrotranslocation of WT Bax, but not tethered Bax, from the mitochondria into the cytoplasm of healthy cells. Bax retrotranslocation depends on prosurvival Bcl-2 family proteins, and inhibition of retrotranslocation correlates with Bax accumulation on the mitochondria. We propose that Bcl-x(L) inhibits and maintains Bax in the cytosol by constant retrotranslocation of mitochondrial Bax.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Ocular Pharmacology and Physiology (Neutzner/Meyer)
UniBasel Contributors:Neutzner, Albert
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:0092-8674
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:08 May 2015 08:45

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