ArticleNature communications2020
MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers, 1 of them a synthesis that pooled it.
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Who cites it
218 citing papers in PubMed, 1 synthesis or guideline pooled it, 345 citations in OpenAlex.
- Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Engineered human induced pluripotent stem cell models reveal altered podocytogenesis in congenital heart disease-associated SMAD2 mutations.Nature biomedical engineering · 2026Article
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- RIPK3's shape-shifting scaffold: how kinase domain conformation fine-tunes necroptosis.Cell death and differentiation · 2026Article
- The PANoptosis hypothesis examined.Nature reviews. Molecular cell biology · 2026Article
- Structural and molecular principles of DAMP biology.Nature structural & molecular biology · 2026Review
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Malondialdehyde epitopes exposed on dying cells are potent modulators of complement activity and efferocytosis.Journal of lipid research · 2026Article
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.Nature communications · 2026Article
- Necroptosis is a key contributor to impaired cardiac repair following myocardial infarction.Cell death & disease · 2026Article
- Phosphatidylinositol (PI)-mediated release of LDH might be due to increased interaction of NINJ1 with membrane lipids based on PI accumulation in the granulosa cell membrane.Irish journal of medical science · 2026Article
- ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.Cell reports · 2026Article
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- Identification of human MLKL Cys184 and HSPBP1 Cys201 as novel cellular targets for necroptosis.Cell death & disease · 2026Article
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Cryo-Structural Insights into Enzymatic Peptide Self-Assembly Driving Extrinsic Lytic Cell Death.Journal of the American Chemical Society · 2026Article
- Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis.Cell reports · 2026Article
158 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. RIPK3-mediated phosphorylation is thought to initiate MLKL oligomerization, membrane translocation and membrane disruption, although the precise choreography of events is incompletely understood. Here, we use single-cell imaging approaches to map the chronology of endogenous human MLKL activation during necroptosis. During the effector phase of necroptosis, we observe that phosphorylated MLKL assembles into higher order species on presumed cytoplasmic necrosomes. Subsequently, MLKL co-traffics with tight junction proteins to the cell periphery via Golgi-microtubule-actin-dependent mechanisms. MLKL and tight junction proteins then steadily co-accumulate at the plasma membrane as heterogeneous micron-sized hotspots. Our studies identify MLKL trafficking and plasma membrane accumulation as crucial necroptosis checkpoints. Furthermore, the accumulation of phosphorylated MLKL at intercellular junctions accelerates necroptosis between neighbouring cells, which may be relevant to inflammatory bowel disease and other necroptosis-mediated enteropathies.
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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.