Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737 |
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Institution: | 1. INRA, UMR 1224 Ecobiop, Pôle d''Hydrobiologie, Quartier Ibarron, 64310, Saint Pée sur Nivelle, France;2. UPPA, UMR 1224 Ecobiop, UFR des Sciences de la Côte Basque, allée du parc Montaury, 64600 Anglet, France |
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Abstract: | 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-xLΔC, 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. |
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Keywords: | Apoptosis Bcl-2 family Mitochondria BH3-mimetics |
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