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Membrane damage by MBP-1 is mediated by pore formation and amplified by mtDNA [Elektronski vir]Gigon, Lea ...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.Vir: Cell reports [Elektronski vir]. - ISSN 2211-1247 (Vol. 43, iss. [article no.] 114084, 2024, str. 1-23, [1-9 pril.])Vrsta gradiva - e-članek ; neleposlovje za odrasleLeto - 2024Jezik - angleškiCOBISS.SI-ID - 193330435
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https://www.cell.com/action/showPdf?pii=S2211-1247%2824%2900412-1Extended PDF [8 MB]
https://www.cell.com/action/showPdf?pii=S2211-1247%2824%2900412-1Standard PDF [5 MB]
DOI
Avtor
Gigon, Lea |
Müller, Philipp, medicina |
Haenni, Beat |
Iacovache, Ioan |
Barbo, Maruša |
Gosheva, Gordana |
Yousefi, Shida |
Soragni, Alice |
Ballmoos, Christoph von |
Zuber, Benoît
Teme
cell biology |
molecular biology |
DNA methylation |
eosinophils |
extracellular trap |
major basic protein |
mitochondrial DNA |
pore formation |
biologija celice |
molekularna biologija |
metilacija DNA |
eozinofili |
zunajcelična past |
glavne osnove beljakovin |
mitohondrijska DNA |
nastanek por
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Gigon, Lea | ![]() |
Müller, Philipp, medicina | ![]() |
Haenni, Beat | ![]() |
Iacovache, Ioan | ![]() |
Barbo, Maruša | 57041 |
Gosheva, Gordana | ![]() |
Yousefi, Shida | ![]() |
Soragni, Alice | ![]() |
Ballmoos, Christoph von | ![]() |
Zuber, Benoît | ![]() |
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