title: Bcl-xL stimulates Bax relocation to mitochondria and primes cells to ABT-737.
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.
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Thibaud T
authors: TT
authors: Renault
authors: New-York University, Department of Basic Sciences, College of Dentistry, New-York, NY 10010, USA.
authors: Oscar
authors: O
authors: Teijido
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Florent
authors: F
authors: Missire
authors: New-York University, Department of Basic Sciences, College of Dentistry, New-York, NY 10010, USA.
authors: Yogesh Tengarai
authors: YT
authors: Ganesan
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Gisèle
authors: G
authors: Velours
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Hubert
authors: H
authors: Arokium
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Florian
authors: F
authors: Beaumatin
authors: California State University of Fresno, Department of Chemistry, 2555 E. San Ramon, Fresno, CA 93740, USA.
authors: Raul
authors: R
authors: Llanos
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Axel
authors: A
authors: Athané
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Nadine
authors: N
authors: Camougrand
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
authors: Muriel
authors: M
authors: Priault
authors: Merck Serono S.A., Geneva Research Center, Department of Protein and Cell Sciences, 9 Chemin des Mines, 1202 Geneva, Switzerland.
authors: Bruno
authors: B
authors: Antonsson
authors: New-York University, Department of Basic Sciences, College of Dentistry, New-York, NY 10010, USA; California State University of Fresno, Department of Chemistry, 2555 E. San Ramon, Fresno, CA 93740, USA. Electronic address: ldejean@csufresno.edu.
authors: Laurent M
authors: LM
authors: Dejean
authors: CNRS, Université de Bordeaux, UMR5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France. Electronic address: manon@ibgc.cnrs.fr.
authors: Stéphen
authors: S
authors: Manon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002460:Cell Line; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009596:Nitrophenols / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D055503:Protein Multimerization; D021381:Protein Transport; D012441:Saccharomyces cerevisiae; D013449:Sulfonamides / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: C501332:ABT-737; D000970:Antineoplastic Agents; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010879:Piperazines; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
keywords: Apoptosis; BH3-mimetics; Bcl-2 family; Mitochondria