ArticleCell death and differentiation2024
MLKL polymerization-induced lysosomal membrane permeabilization promotes necroptosis.
Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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Who cites it
55 citing papers in PubMed, 63 citations in OpenAlex.
- β-Adducin Restrains PLA2G4A-Dependent Lysosomal Membrane Permeabilization and Neuronal Death in Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MLKL regulates intracellular trafficking of neutrophil elastase to promote lung epithelial cell senescence.American journal of respiratory cell and molecular biology · 2026Article
- FDX1-short proteoform induces caspase-independent cell death in tumor cells.Cell death and differentiation · 2026Article
- African swine fever virus impairs porcine alveolar macrophages bactericidal function by disrupting lysosomal acidification and cathepsin activity.PLoS pathogens · 2026Article
- Structural and molecular principles of DAMP biology.Nature structural & molecular biology · 2026Review
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Review
- Experimental Characterization Combined with Computational Network Analysis of Metabolites Associated with Chrysanthemum morifolium-derived exosome-like Nanoparticles in Predicting Potential AKI-relevant Targets.Cell biochemistry and biophysics · 2026Article
- Research Progress on NINJ1-Mediated Plasma Membrane Rupture Regulation of Pathogen Infection Process.International journal of molecular sciences · 2026Review
- Therapeutic Effects of Glycyrrhizic Acid on Dry Eye Disease: Targeting Pyroptosis, Oxidative Stress, and Epithelial Barrier Dysfunction.International journal of molecular sciences · 2026Article
- The role and mechanism of TNFRSF21 in promoting necroptosis of vascular endothelial cells and inducing vascular leakage in sepsis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Lipopolysaccharides Drive Proinflammatory Extracellular Vesicle Secretion in Coronary Artery Endothelial Cells via Noncanonical Inflammasome Activation.Cellular and molecular life sciences : CMLS · 2026Article
- Agonal cell resuscitation strategy to promote tissue repair.Nature communications · 2026Article
- TOLLIP targets GSDME-NT-carrying endocytic vesicles for autophagy to regulate pyroptosis and chemotherapy efficacy.Nature cell biology · 2026Article
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- Metabolic syndrome necroptosis: disease implications and therapeutic targeting.Journal of physiology and biochemistry · 2026Review
- Lys-ing the Resistance: Targeting Lysosomes to Overcome Chemoresistance in Ovarian Cancer.Current oncology reports · 2026Review
- Pathogen-Induced Lysosomal Membrane Permeabilization: A Critical Interface Between Host Defense and Cell Death.International journal of molecular sciences · 2026Review
- Intracellular CaBMC molecular and cell biology · 2026Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Mixed lineage kinase-like protein (MLKL) forms amyloid-like polymers to promote necroptosis; however, the mechanism through which these polymers trigger cell death is not clear. We have determined that activated MLKL translocates to the lysosomal membrane during necroptosis induction. The subsequent polymerization of MLKL induces lysosome clustering and fusion and eventual lysosomal membrane permeabilization (LMP). This LMP leads to the rapid release of lysosomal contents into the cytosol, resulting in a massive surge in cathepsin levels, with Cathepsin B (CTSB) as a significant contributor to the ensuing cell death as it cleaves many proteins essential for cell survival. Importantly, chemical inhibition or knockdown of CTSB protects cells from necroptosis. Furthermore, induced polymerization of the MLKL N-terminal domain (NTD) also triggers LMP, leading to CTSB release and subsequent cell death. These findings clearly establish the critical role of MLKL polymerization induced lysosomal membrane permeabilization (MPI-LMP) in the process of necroptosis.
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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.