ArticleCell research2016
MLKL forms cation channels.
Article in Cell research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 1 of them a synthesis that pooled it.
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Who cites it
123 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 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
- Review
- Review
- A WEEV 6K viroporin activates MLKL-dependent necroptosis to drive inflammatory injury.Cell death discovery · 2026Article
- Study on the Modes of Cell Death in Lung Cancer Epithelial Cells During Acute EBV Infection Using a Co-Culture Model.Thoracic cancer · 2026Article
- Regulated cell death in fungi from a comparative immunology perspective.Cell death and differentiation · 2026Review
- Sodium disrupts mitochondrial energy metabolism to execute NECSO.Nature communications · 2025Article
- Distinct mechanisms of cell in breast cancer and their clinical implication.Cell biology and toxicology · 2025Review
- PANoptosis: A novel therapeutic target in kidney disease (Review).International journal of molecular medicine · 2025Review
- Cracking the code of cancer immunotherapy resistance: emerging roles of pyroptosis and necroptosis.Journal of experimental & clinical cancer research : CR · 2025Review
- Induced necroptosis limitsInfection and immunity · 2025Article
- The B169L protein of African swine fever virus functions as a viroporin that activates the calcium-mediated inflammasome.PLoS pathogens · 2025Article
- CHMP4C promotes pancreatic cancer progression by inhibiting necroptosis via the RIPK1/RIPK3/MLKL pathway.Journal of advanced research · 2025Article
- Role of RIPK1/RIPK3/MLKL signalling pathway in sepsis-associated acute kidney injury.Experimental physiology · 2025Review
- Targeting metalloptosis in tumor therapy: from molecular mechanisms to application of metal nanoparticles.Molecular cancer · 2025Review
- Disrupting membranes, controlling cell fate: the role of pore-forming proteins in cell death and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Integrated transcriptomics and metabolomics confirms the oxidative stress mechanism of hypothermia-induced neuronal necroptosis.Cellular & molecular biology letters · 2025Article
- The Multifaceted Role of Calcium Signaling in Regulated Necrosis.Biomolecules · 2025Review
- Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor necrosis factor-induced necroptosis. Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption. However, our knowledge of how MLKL functions on membrane remains very limited. Here we demonstrate that MLKL forms cation channels that are permeable preferentially to Mg(2+) rather than Ca(2+) in the presence of Na(+) and K(+). Moreover, the N-terminal domain containing six helices (H1-H6) is sufficient to form channels. Using the substituted cysteine accessibility method, we further determine that helix H1, H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. The Mg(2+)-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg(2+)-permeable channels and thus establish MLKL as a novel class of cation channels.
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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.