ArticleGenes & development2016
Inactivation of prosurvival Bcl-2 proteins activates Bax/Bak through the outer mitochondrial membrane.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 312 citations in OpenAlex.
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- Effects of Pre- and Post-treatment of Idebenone on the Side Effects of the Chemotherapy Model with Cyclophosphamide in the Rat Ovary.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Avoiding Mitochondrial Apoptosis by the Bcl-2-Driven Bax Oligomerization on Membrane Surfaces.ACS chemical biology · 2026Article
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- Activator of apoptosis harakiri (HRK) localisation at mitochondria alters mitochondrial morphology independently of other BCL-2 proteins.The FEBS journal · 2026Article
- PANoptosis and mitochondrial regulatory mechanisms in cerebral ischemia-reperfusion injury.Frontiers in physiology · 2026Review
- Sodium butyrate induces mitochondrial pathway apoptosis in liver cancer via ATF4/SLC7A11-mediated ferroptosis.PloS one · 2026Article
- HSP90α and KLK6 Co-Regulate Stress-Induced Prostate Cancer Cell Motility.bioRxiv : the preprint server for biology · 2025Article
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- Dietary choline-derived Trimethylamine N-oxide impairs hippocampal neuronal function via PANoptosis activation.NPJ science of food · 2025Article
- Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.Nature reviews. Clinical oncology · 2025Review
- Role of exosomal non‑coding RNAs in cancer‑associated fibroblast‑mediated therapy resistance (Review).International journal of oncology · 2025Review
- The BCL-2 protein family: from discovery to drug development.Cell death and differentiation · 2025Review
- Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.Molecular neurobiology · 2025Review
- Collaborative orchestration of BH3-only proteins governs Bak/Bax-dependent hepatocyte apoptosis under antiapoptotic protein-deficiency in mice.Cell death and differentiation · 2025Article
- Structural basis of BAK sequestration by MCL-1 in apoptosis.Molecular cell · 2025Article
- HPMA Copolymers: A Versatile Platform for Targeted Peptide Drug Delivery.Biomolecules · 2025Review
118 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The mechanism of Bax/Bak activation remains a central question in mitochondria-dependent apoptotic signaling. While it is established that all proapoptotic Bcl-2 homology 3 (BH3)-only proteins bind and neutralize the anti-apoptotic Bcl-2 family proteins, how this neutralization leads to Bax/Bak activation has been actively debated. Here, genome editing was used to generate cells deficient for all eight proapoptotic BH3-only proteins (OctaKO) and those that lack the entire Bcl-2 family (Bcl-2 allKO). Although the OctaKO cells were resistant to most apoptotic stimuli tested, they underwent Bax/Bak-dependent and p53/Rb-independent apoptosis efficiently when both Bcl-xL and Mcl-1, two anti-apoptotic Bcl-2 proteins, were inactivated or eliminated. Strikingly, when expressed in the Bcl-2 allKO cells, both Bax and Bak spontaneously associated with the outer mitochondrial membrane (OMM) through their respective helix 9, and this association triggered their homo-oligomerization/activation. Together, these results strongly suggest that the OMM, not BH3-only proteins or p53/Rb, is the long-sought-after direct activator of Bax/Bak following BH3-only-mediated neutralization of anti-apoptotic Bcl-2 proteins.
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Registered trials
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.