ArticleCell death & disease2021
The necroptotic cell death pathway operates in megakaryocytes, but not in platelet synthesis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Converging Molecular Mechanisms of Nucleated Cell Death Pathways and Procoagulant Platelet Formation.Cells · 2025Review
- Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer.Journal of translational medicine · 2025Review
- A modern overview of the process of platelet formation (thrombocytopoiesis) and its dependence on several factors.Biochemia medica · 2024Review
- Mitochondria and cell death.Nature cell biology · 2024Review
- Ayurvedic preparations of Raudra Rasa inhibit agonist-mediated platelet activation and restrict thrombogenicity without affecting cell viability.FEBS open bio · 2023Article
- Platelet ITGA2B inhibits caspase-8 and Rip3/Mlkl-dependent platelet death though PTPN6 during sepsis.iScience · 2023Article
- Necroptosis executioner MLKL plays pivotal roles in agonist-induced platelet prothrombotic responses and lytic cell death in a temporal order.Cell death and differentiation · 2023Article
- Interplay between Cell Death and Cell Proliferation Reveals New Strategies for Cancer Therapy.International journal of molecular sciences · 2022Review
- Programmed Cell Death Tunes Tumor Immunity.Frontiers in immunology · 2022Review
- Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword.International journal of molecular sciences · 2021Review
- The Role of the Key Effector of Necroptotic Cell Death, MLKL, in Mouse Models of Disease.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is a pro-inflammatory cell death program executed by the terminal effector, mixed lineage kinase domain-like (MLKL). Previous studies suggested a role for the necroptotic machinery in platelets, where loss of MLKL or its upstream regulator, RIPK3 kinase, impacted thrombosis and haemostasis. However, it remains unknown whether necroptosis operates within megakaryocytes, the progenitors of platelets, and whether necroptotic cell death might contribute to or diminish platelet production. Here, we demonstrate that megakaryocytes possess a functional necroptosis signalling cascade. Necroptosis activation leads to phosphorylation of MLKL, loss of viability and cell swelling. Analyses at steady state and post antibody-mediated thrombocytopenia revealed that platelet production was normal in the absence of MLKL, however, platelet activation and haemostasis were impaired with prolonged tail re-bleeding times. We conclude that MLKL plays a role in regulating platelet function and haemostasis and that necroptosis signalling in megakaryocytes is dispensable for platelet production.
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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.