ArticleMolecular and cellular biology2007
Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 316 citations in OpenAlex.
- Interplay Among Synaptic Glutamate Release and Excitotoxicity: Neuronal Damage and Graphene-Based Materials Related Protection.Life (Basel, Switzerland) · 2025Review
- RNase H-sensitive accumulation of APOBEC3B in a nucleolus after DNA damage.Bioscience reports · 2025Article
- AMPK Limits MNNG-Induced Parthanatos by Inhibiting BH3-Only Protein Bim.International journal of molecular sciences · 2025Article
- Deacetylation of nuclear AIF provides a braking mechanism for caspase-independent chromatinolysis and necrotic brain injury.Communications biology · 2025Article
- Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells.Open life sciences · 2024Article
- Protease-independent control of parthanatos by HtrA2/Omi.Cellular and molecular life sciences : CMLS · 2023Article
- Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions.Cell death and differentiation · 2023Review
- Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies.Frontiers in neuroscience · 2023Review
- Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases.International journal of molecular sciences · 2022Review
- Mitochondria signaling pathways in allergic asthma.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2022Review
- The key players of parthanatos: opportunities for targeting multiple levels in the therapy of parthanatos-based pathogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Mitochondrial Targeting of Amyloid-β Protein Precursor Intracellular Domain Induces Hippocampal Cell Death via a Mechanism Distinct from Amyloid-β.Journal of Alzheimer's disease : JAD · 2022Article
- Mitochondria Related Cell Death Modalities and Disease.Frontiers in cell and developmental biology · 2022Review
- Cyclophilin D Regulates the Nuclear Translocation of AIF, Cardiac Endothelial Cell Necroptosis and Murine Cardiac Transplant Injury.International journal of molecular sciences · 2021Article
- Profilin 1 and Mitochondria-Partners in the Pathogenesis of Coronary Artery Disease?International journal of molecular sciences · 2021Review
- Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells.Brain sciences · 2020Article
- Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.Cancers · 2020Review
- Mitochondrial AIF loss causes metabolic reprogramming, caspase-independent cell death blockade, embryonic lethality, and perinatal hydrocephalus.Molecular metabolism · 2020Article
- Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions.Biomedicines · 2020Review
- Targeting necroptosis in anticancer therapy: mechanisms and modulators.Acta pharmaceutica Sinica. B · 2020Review
84 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alkylating DNA damage induces a necrotic type of programmed cell death through the poly(ADP-ribose) polymerases (PARP) and apoptosis-inducing factor (AIF). Following PARP activation, AIF is released from mitochondria and translocates to the nucleus, where it causes chromatin condensation and DNA fragmentation. By employing a large panel of gene knockout cells, we identified and describe here two essential molecular links between PARP and AIF: calpains and Bax. Alkylating DNA damage initiated a p53-independent form of death involving PARP-1 but not PARP-2. Once activated, PARP-1 mediated mitochondrial AIF release and necrosis through a mechanism requiring calpains but not cathepsins or caspases. Importantly, single ablation of the proapoptotic Bcl-2 family member Bax, but not Bak, prevented both AIF release and alkylating DNA damage-induced death. Thus, Bax is indispensable for this type of necrosis. Our data also revealed that Bcl-2 regulates N-methyl-N'-nitro-N'-nitrosoguanidine-induced necrosis. Finally, we established the molecular ordering of PARP-1, calpains, Bax, and AIF activation, and we showed that AIF downregulation confers resistance to alkylating DNA damage-induced necrosis. Our data shed new light on the mechanisms regulating AIF-dependent necrosis and support the notion that, like apoptosis, necrosis could be a highly regulated cell death program.
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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.