ArticleProceedings of the National Academy of Sciences of the United States of America2012
Bax regulates primary necrosis through mitochondrial dynamics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 2 of them syntheses 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
172 citing papers in PubMed, 2 syntheses or guidelines pooled it, 286 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- The romantic history of signaling pathway discovery in cell death: an updated review.Molecular and cellular biochemistry · 2024Pooled it
- Mitochondrial oxidative stress, calcium and dynamics in cardiac ischaemia-reperfusion injury.The Journal of physiology · 2026Review
- Mitochondrial Quality Control in Age-Related Diseases: From Molecular Architecture to Precision Therapeutics.Antioxidants (Basel, Switzerland) · 2026Review
- Reverse engineering of BNIP3 identifies a mitochondrial protective peptide.Nature communications · 2026Article
- Synaptotagmin-7 drives stress-induced cardiomyocyte necroptosis via the p53-Bak-mPTP axis.Theranostics · 2026Article
- Qing-Xin-Jie-Yu granule prevents myocardial infarction-induced apoptosis via inhibition of p38 MAPK pathway.Frontiers in cardiovascular medicine · 2026Article
- Yeast NatB Regulates Cell Death of Bax-Expressing Cells.Biomolecules · 2025Article
- Review
- Review
- Regulated Cell Death in Myocardial Infarction.Circulation research · 2025Article
- Death-Associated Protein 3 Triggers Intrinsic Apoptosis via Miro1 Upon Inducing Intracellular Calcium Changes.MedComm · 2025Article
- Senolysis by GLS1 Inhibition Ameliorates Kidney Aging by Inducing Excessive mPTP Opening Through MFN1.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Retinol-binding protein 4 in skeletal and cardiac muscle: molecular mechanisms, clinical implications, and future perspectives.Frontiers in cell and developmental biology · 2025Review
- Targeting Lactylation Offers Therapy to Reverse Cell Death Resistance.Drug design, development and therapy · 2025Review
- Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.Frontiers in pharmacology · 2025Article
- FTO Alleviates Hepatic Ischemia-Reperfusion Injury by Regulating Apoptosis and Autophagy.Gastroenterology research and practice · 2025Article
- Role of layilin in regulating mitochondria-mediated apoptosis: a study on B cell lymphoma (BCL)-2 family proteins.BMC molecular and cell biology · 2024Article
- Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges.Acta pharmaceutica Sinica. B · 2024Review
- NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression.Cell death discovery · 2024Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
The defining event in apoptosis is mitochondrial outer membrane permeabilization (MOMP), allowing apoptogen release. In contrast, the triggering event in primary necrosis is early opening of the inner membrane mitochondrial permeability transition pore (mPTP), precipitating mitochondrial dysfunction and cessation of ATP synthesis. Bcl-2 proteins Bax and Bak are the principal activators of MOMP and apoptosis. Unexpectedly, we find that deletion of Bax and Bak dramatically reduces necrotic injury during myocardial infarction in vivo. Triple knockout mice lacking Bax/Bak and cyclophilin D, a key regulator of necrosis, fail to show further reduction in infarct size over those deficient in Bax/Bak. Absence of Bax/Bak renders cells resistant to mPTP opening and necrosis, effects confirmed in isolated mitochondria. Reconstitution of these cells or mitochondria with wild-type Bax, or an oligomerization-deficient mutant that cannot support MOMP and apoptosis, restores mPTP opening and necrosis, implicating distinct mechanisms for Bax-regulated necrosis and apoptosis. Both forms of Bax restore mitochondrial fusion in Bax/Bak-null cells, which otherwise exhibit fragmented mitochondria. Cells lacking mitofusin 2 (Mfn2), which exhibit similar fusion defects, are protected to the same extent as Bax/Bak-null cells. Conversely, restoration of fused mitochondria through inhibition of fission potentiates mPTP opening in the absence of Bax/Bak or Mfn2, indicating that the fused state itself is critical. These data demonstrate that Bax-driven fusion lowers the threshold for mPTP opening and necrosis. Thus, Bax and Bak play wider roles in cell death than previously appreciated and may be optimal therapeutic targets for diseases that involve both forms of cell death.
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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.