ArticleThe Journal of biological chemistry2015
The BH4 domain of anti-apoptotic Bcl-XL, but not that of the related Bcl-2, limits the voltage-dependent anion channel 1 (VDAC1)-mediated transfer of pro-apoptotic Ca2+ signals to mitochondria.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 128 citations in OpenAlex.
- Intermembrane coupling between Bcl-xL and the IPCell reports · 2026Article
- A pore is a pore is a pore (or a hub?): VDAC oligomerization in mitochondrial connectivity and modulation.Biochemical Society transactions · 2026Review
- Spatiotemporal Ca2+ nanodomain remodeling at MERCS regulates mitochondrial proteostasis.Protein & cell · 2026Article
- A2-pancortins interact with Bcl-xL and WAVE1 to promote mitochondria-ER contact sites (MERCs) and exacerbate mitochondrial calcium elevation to mediate cell death in stroke.Scientific reports · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- Role of VDAC1 in hepatocyte apoptosis during acute liver injury in rats induced by obstructive jaundice.Iranian journal of basic medical sciences · 2025Article
- ER-mitochondria distance is a critical parameter for efficient mitochondrial CaCommunications biology · 2024Article
- BMP receptor 2 inhibition regulates mitochondrial bioenergetics to induce synergistic cell death with BCL-2 inhibitors in leukemia and NSLC cells.Research square · 2024Article
- BCL2L13 at endoplasmic reticulum-mitochondria contact sites regulates calcium homeostasis to maintain skeletal muscle function.iScience · 2024Article
- MIRO-1 interacts with VDAC-1 to regulate mitochondrial membrane potential in Caenorhabditis elegans.EMBO reports · 2023Article
- Synergistic mechanism between the endoplasmic reticulum and mitochondria and their crosstalk with other organelles.Cell death discovery · 2023Review
- Mitochondria signaling pathways in allergic asthma.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2022Review
- Bcl-xL acts as an inhibitor of IPCell death and differentiation · 2022Article
- Mitochondrial CaInternational journal of molecular sciences · 2022Review
- ER-mitochondria contact sites; a multifaceted factory for CaFrontiers in cell and developmental biology · 2022Review
- Mitochondrial dysfunction in perinatal asphyxia: role in pathogenesis and potential therapeutic interventions.Molecular and cellular biochemistry · 2021Review
- Balancing ER-Mitochondrial CaTrends in cell biology · 2021Review
- Review
- Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation.Journal of experimental & clinical cancer research : CR · 2021Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive Ca(2+) fluxes from the endoplasmic reticulum to the mitochondria result in apoptotic cell death. Bcl-2 and Bcl-XL proteins exert part of their anti-apoptotic function by directly targeting Ca(2+)-transport systems, like the endoplasmic reticulum-localized inositol 1,4,5-trisphosphate receptors (IP3Rs) and the voltage-dependent anion channel 1 (VDAC1) at the outer mitochondrial membranes. We previously demonstrated that the Bcl-2 homology 4 (BH4) domain of Bcl-2 protects against Ca(2+)-dependent apoptosis by binding and inhibiting IP3Rs, although the BH4 domain of Bcl-XL was protective independently of binding IP3Rs. Here, we report that in contrast to the BH4 domain of Bcl-2, the BH4 domain of Bcl-XL binds and inhibits VDAC1. In intact cells, delivery of the BH4-Bcl-XL peptide via electroporation limits agonist-induced mitochondrial Ca(2+) uptake and protects against staurosporine-induced apoptosis, in line with the results obtained with VDAC1(-/-) cells. Moreover, the delivery of the N-terminal domain of VDAC1 as a synthetic peptide (VDAC1-NP) abolishes the ability of BH4-Bcl-XL to suppress mitochondrial Ca(2+) uptake and to protect against apoptosis. Importantly, VDAC1-NP did not affect the ability of BH4-Bcl-2 to suppress agonist-induced Ca(2+) release in the cytosol or to prevent apoptosis, as done instead by an IP3R-derived peptide. In conclusion, our data indicate that the BH4 domain of Bcl-XL, but not that of Bcl-2, selectively targets VDAC1 and inhibits apoptosis by decreasing VDAC1-mediated Ca(2+) uptake into the mitochondria.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.