20.500.12556/RUL-175845 Membrane damage by MBP-1 is mediated by pore formation and amplified by mtDNA Eosinophils play a crucial role in host defense while also contributing to immunopathology through the release of inflammatory mediators. Characterized by distinctive cytoplasmic granules, eosinophils securely store and rapidly release various proteins exhibiting high toxicity upon extracellular release. Among these, major basic protein 1 (MBP-1) emerges as an important mediator in eosinophil function against pathogens and in eosinophil-associated diseases. While MBP-1 targets both microorganisms and host cells, its precise mechanism remains elusive. We demonstrate that formation of small pores by MBP-1 in lipid bilayers induces membrane permeabilization and disrupts potassium balance. Additionally, we reveal that mitochondrial DNA (mtDNA) present in eosinophil extracellular traps (EETs) amplifies MBP-1 toxic effects, underscoring the pivotal role of mtDNA in EETs. Furthermore, we present evidence indicating that absence of CpG methylation in mtDNA contributes to the regulation of MBP-1-mediated toxicity. Taken together, our data suggest that the mtDNA scaffold within extracellular traps promotes MBP-1 toxicity. extracellular trap eosinophils major basic protein DNA methylation mitochondrial DNA poreformation zunajcelična past eozinofili glavna bazična beljakovina metilacija DNA tvorba por mitohondrijske DNA celična biologija molekularna biologija true false true Angleški jezik Slovenski jezik Članek v reviji 2025-11-11 08:38:38 2025-11-11 08:38:43 2025-12-15 04:05:41 0000-00-00 00:00:00 2025 0 0 23 str. iss. 4, [article no.] 114084 Vol. 44 Aug. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 576.3+577.2 2211-1247 10.1016/j.celrep.2024.114084 248366339 1-s2.0-S2211124724004121-main.pdf 1-s2.0-S2211124724004121-main.pdf 1 46B6756C0A0DDBB621DAA6937BFF97BC ae9c3725042bb7ffa05f9f9b90e7497e8305049b254106354f6bfb29a2100812 abfd4ace-bed1-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=221747 https://www.sciencedirect.com/science/article/pii/S2211124724004121 1 1f71408a-bed1-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=221745 https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00412-1 1 1f9dd9de-bed1-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=221746 Fakulteta za farmacijo 0 0 0