ArticleThe Journal of experimental medicine2003
The apoptosome pathway to caspase activation in primary human neutrophils exhibits dramatically reduced requirements for cytochrome C.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 98 citations in OpenAlex.
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- Histone lactylation exacerbates acute lung injury in septic mice by promoting ferroptosis in pulmonary microvascular endothelial cells.Burns & trauma · 2025Article
- Pseudorabies virus UL38 attenuates the cGAS-STING signaling pathway by recruiting Tollip to promote STING for autophagy degradation.Virology journal · 2024Article
- Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
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- Pyroptosis in neutrophils: Multimodal integration of inflammasome and regulated cell death signaling pathways.Immunological reviews · 2023Review
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- Neutrophils: Many Ways to Die.Frontiers in immunology · 2021Review
- Neutrophils in innate immunity and systems biology-level approaches.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Article
- Implementing Patient-Derived Xenografts to Assess the Effectiveness of Cyclin-Dependent Kinase Inhibitors in Glioblastoma.Cancers · 2019Article
- Post-Translational Modifications in NETosis and NETs-Mediated Diseases.Biomolecules · 2019Review
- Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation.Veterinary medicine (Auckland, N.Z.) · 2019Article
- Inflammation Resolution and the Induction of Granulocyte Apoptosis by Cyclin-Dependent Kinase Inhibitor Drugs.Frontiers in pharmacology · 2019Review
- Acute CD47 Blockade During Ischemic Myocardial Reperfusion Enhances Phagocytosis-Associated Cardiac Repair.JACC. Basic to translational science · 2017Article
- Necrostatin-1 enhances the resolution of inflammation by specifically inducing neutrophil apoptosis.Oncotarget · 2016Article
- Mcl-1 is vital for neutrophil survival.Immunologic research · 2015Review
- Bacteria induce prolonged PMN survival via a phosphatidylcholine-specific phospholipase C- and protein kinase C-dependent mechanism.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caspase activation is a central event in numerous forms of apoptosis and results in the proteolytic degradation of multiple substrate proteins that contribute to the apoptotic phenotype. An important route to caspase activation proceeds via assembly of the "apoptosome" as a result of the cell stress-associated release of mitochondrial cytochrome c. Previous studies have shown that primary neutrophils are largely incapable of mitochondrial respiration, suggesting that these cells either lack functional mitochondria or possess a defective respiratory chain. This prompted us to examine whether neutrophils retain an intact cytochrome c/apoptotic protease-activating factor 1 (Apaf-1) pathway to caspase activation and apoptosis. We show that primary human neutrophils contain barely detectable levels of cytochrome c as well as other mitochondrial proteins. Surprisingly, neutrophil cell-free extracts readily supported Apaf-1-dependent caspase activation, suggesting that these cells may assemble cytochrome c-independent apoptosomes. However, further analysis revealed that the trace amount of cytochrome c present in neutrophils is both necessary and sufficient for Apaf-1-dependent caspase activation in these cells. Thus, neutrophils have a lowered threshold requirement for cytochrome c in the Apaf-1-dependent cell death pathway. These observations suggest that neutrophils retain cytochrome c for the purpose of assembling functional apoptosomes rather than for oxidative phosphorylation.
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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.