Mediation of the Antiapoptotic Activity of Bcl-xL Protein upon Interaction with VDAC1 Protein

Arbel, Nir; Ben-Hail, Danya; Shoshan‐Barmatz, Varda

doi:10.1074/jbc.m112.345918

Cited by 151 publications

(198 citation statements)

References 59 publications

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“…BCLXL interactions for cell survival are not limited to the BCL2 family of proteins. It also interacts with VDAC1 for cell survival as shown by the studies in human cell line [31].…”

Section: Introductionmentioning

confidence: 96%

Candidate gene expression patterns in rabbit preimplantation embryos developed in vivo and in vitro

Gibence

Brahmasani

Mahesh

et al. 2014

J Assist Reprod Genet

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Purpose The levels and timing of expression of genes like BCLXL, HDAC1 and pluripotency marker genes namely, OCT4, SOX2, NANOG and KLF4 are known to influence preimplantation embryo development. Despite this information, precise understanding of their influence during preimplantation embryo development is lacking. The present study attempts to compare the expression of these genes in the in vivo and in vitro developed preimplantation embryos. Methods The in vivo and in vitro developed rabbit embryos collected at distinct developmental stages namely, pronuclear, 2 cell, 4 cell, 8 cell, 16 cell, Morula and blastocyst were compared at the transcriptional and translational levels using Real Time PCR and immunocytochemical studies respectively. Results The study establishes the altered levels of candidate genes at the transcriptional level and translational level with reference to the zygotic genome activation (ZGA) phase of embryo development in the in vivo and in vitro developed embryos. The expression of OCT4, KLF4, NANOG and SOX2 genes were higher in the in vitro developed embryos whereas and HDAC1 was lower. BCLXL expression had its peak at ZGA in in vivo developed embryos. Protein expression of all the candidate genes was observed in the embryos. BCLXL, KLF4 and NANOG exhibited diffused localisation whereas HDAC1, OCT4, and SOX2 exhibited nuclear localisation. Conclusions This study leads to conclude that BCLXL peak expression at the ZGA phase may be a requirement for embryo development. Further expression of all the candidate genes was influenced by ZGA phase of development at the transcript level, but not at the protein level.

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“…BCLXL interactions for cell survival are not limited to the BCL2 family of proteins. It also interacts with VDAC1 for cell survival as shown by the studies in human cell line [31].…”

Section: Introductionmentioning

confidence: 96%

Candidate gene expression patterns in rabbit preimplantation embryos developed in vivo and in vitro

Gibence

Brahmasani

Mahesh

et al. 2014

J Assist Reprod Genet

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“…At the level of the endoplasmic reticulum (ER), the main intracellular Ca 2+ store, Bcl-2-family members target the inositol 1,4,5-trisphosphate (IP 3 ) receptor (IP 3 R) (Monaco et al, 2012a;Oakes et al, 2005;Rong et al, 2008;White et al, 2005), sarco/endoplasmic-reticulum Ca 2+ -ATPases (SERCAs) (Kuo et al, 1998) and Bax inhibitor 1 (BI-1, also known as TMBIM6) (Ahn et al, 2010;Xu and Reed, 1998). At the mitochondrial outer membranes, Bcl-2 proteins target the voltage-dependent anion channels (VDACs) (Arbel and ShoshanBarmatz, 2010;Arbel et al, 2012;Plötz et al, 2012). More recently, Bcl-2 has been shown to regulate plasma-membrane Ca 2+ -ATPase (PMCA) activity (Ferdek et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Bcl-2 binds to and inhibits ryanodine receptors

Vervliet¹,

Decrock²,

Molgó³

et al. 2014

Journal of Cell Science

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The anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein not only counteracts apoptosis at the mitochondria by scaffolding proapoptotic Bcl-2-family members, but also acts at the endoplasmic reticulum, thereby controlling intracellular Ca 2+ dynamics. Bcl-2 inhibits Ca 2+ release by targeting the inositol 1,4,5-trisphosphate receptor (IP 3 R). Sequence analysis has revealed that the Bcl-2-binding site on the IP 3 R displays strong similarity with a conserved sequence present in all three ryanodine receptor (RyR) isoforms. We now report that Bcl-2 co-immunoprecipitated with RyRs in ectopic expression systems and in native rat hippocampi, indicating that endogenous RyR-Bcl-2 complexes exist. Purified RyR domains containing the putative Bcl-2-binding site bound fulllength Bcl-2 in pulldown experiments and interacted with the BH4 domain of Bcl-2 in surface plasmon resonance (SPR) experiments, suggesting a direct interaction. Exogenous expression of fulllength Bcl-2 or electroporation loading of the BH4 domain of Bcl-2 dampened RyR-mediated Ca 2+ release in HEK293 cell models.Finally, introducing the BH4-domain peptide into hippocampal neurons through a patch pipette decreased RyR-mediated Ca 2+ release. In conclusion, this study identifies Bcl-2 as a new inhibitor of RyR-based intracellular Ca 2+ -release channels.

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“…16,32 This role for VDAC2 is seemingly specific for Bak and Bax as the mitochondrial targeting of other Bcl-2 family members including Bcl-x L , Mcl-1 and tBid was not affected by the absence of VDAC2. Recently, Bcl-x L was shown to interact with VDAC1, 33 but not VDAC2, 34 suggesting that other VDAC isoforms may play a role in mitochondrial targeting of these Bcl-2 family proteins.…”

mentioning

confidence: 99%

Bax targets mitochondria by distinct mechanisms before or during apoptotic cell death: a requirement for VDAC2 or Bak for efficient Bax apoptotic function

et al. 2014

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In non-apoptotic cells, Bak constitutively resides in the mitochondrial outer membrane. In contrast, Bax is in a dynamic equilibrium between the cytosol and mitochondria, and is commonly predominant in the cytosol. In response to an apoptotic stimulus, Bax and Bak change conformation, leading to Bax accumulation at mitochondria and Bak/Bax oligomerization to form a pore in the mitochondrial outer membrane that is responsible for cell death. Using blue native-PAGE to investigate how Bax oligomerizes in the mitochondrial outer membrane, we observed that, like Bak, a proportion of Bax that constitutively resides at mitochondria associates with voltage-dependent anion channel (VDAC)2 prior to an apoptotic stimulus. During apoptosis, Bax dissociates from VDAC2 and homo-oligomerizes to form high molecular weight oligomers. In cells that lack VDAC2, constitutive mitochondrial localization of Bax and Bak was impaired, suggesting that VDAC2 has a role in Bax and Bak import to, or stability at, the mitochondrial outer membrane. However, following an apoptotic stimulus, Bak and Bax retained the ability to accumulate at VDAC2-deficient mitochondria and to mediate cell death. Silencing of Bak in VDAC2-deficient cells indicated that Bax required either VDAC2 or Bak in order to translocate to and oligomerize at the mitochondrial outer membrane to efficiently mediate apoptosis. In contrast, efficient Bak homo-oligomerization at the mitochondrial outer membrane and its pro-apoptotic function required neither VDAC2 nor Bax. Even a C-terminal mutant of Bax (S184L) that localizes to mitochondria did not constitutively target mitochondria deficient in VDAC2, but was recruited to mitochondria following an apoptotic stimulus dependent on Bak or upon over-expression of Bcl-x L . Together, our data suggest that Bax localizes to the mitochondrial outer membrane via alternate mechanisms, either constitutively via an interaction with VDAC2 or after activation via interaction with Bcl-2 family proteins.

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Mediation of the Antiapoptotic Activity of Bcl-xL Protein upon Interaction with VDAC1 Protein

Cited by 151 publications

References 59 publications

Candidate gene expression patterns in rabbit preimplantation embryos developed in vivo and in vitro

Candidate gene expression patterns in rabbit preimplantation embryos developed in vivo and in vitro

Bcl-2 binds to and inhibits ryanodine receptors

Bax targets mitochondria by distinct mechanisms before or during apoptotic cell death: a requirement for VDAC2 or Bak for efficient Bax apoptotic function

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