期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 64, 期 -, 页码 136-146出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2015.03.020
关键词
Apoptosis; Bcl-2 family; Mitochondria; BH3-mimetics
资金
- Centre National de la Recherche Scientifique
- Conseil Regional d'Aquitaine
- Association pour la Recherche contre le Cancer
- University of Bordeaux
- Challenge Funds grant from the New-York University
- CSU Fresno
- French Ministry of Research and Technology
Bax cytosol-to-mitochondria translocation is a central event of the intrinsic pathway of apoptosis. Bcl-xL. is an important regulator of this event and was recently shown to promote the retrotranslocation of mitochondrial Bax to the cytosol. The present study identifies a new aspect of the regulation of Bax localization by Bcl-xL: in addition to its role in Bax inhibition and retrotranslocation, we found that, like with Bcl-2, an increase of Bcl-xL expression levels led to an increase of Bax mitochondrial content. This finding was substantiated both in pro-lymphocytic FL5.12 cells and a yeast reporting system. Bcl-xL-dependent increase of mitochondrial Bax is counterbalanced by retrotranslocation, as we observed that Bcl-xL Delta C, which is unable to promote Bax retrotranslocation, was more efficient than the full-length protein in stimulating Bax relocation to mitochondria. Interestingly, cells overexpressing Bcl-xL were more sensitive to apoptosis upon treatment with the BH3-mimetic ABT-737, suggesting that despite its role in Bax inhibition, Bcl-xL also primes mitochondria to permeabilization and cytochrome c release. (C) 2015 Elsevier Ltd. All rights reserved.
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