Membrane damage by MBP-1 is mediated by pore formation and amplified by mtDNA

Gigon, Lea (author), Müller, Philipp (author), Haenni, Beat (author), Iacovache, Ioan (author), Barbo, Maruša (author), Gosheva, Gordana (author), Yousefi, Shida (author), Soragni, Alice (author), Ballmoos, Christoph von (author), Zuber, Benoît (author), Simon, Hans-Uwe (author)

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.

• Language: English
• Keywords: extracellular trap, eosinophils, major basic protein, DNA methylation, mitochondrial DNA, poreformation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 23 str.
• Numbering: Vol. 44, iss. 4, [article no.] 114084
• PID: 20.500.12556/RUL-175845
• UDC: 576.3+577.2
• ISSN on article: 2211-1247
• DOI: 10.1016/j.celrep.2024.114084
• COBISS.SI-ID: 248366339
• Publication date in RUL: 11.11.2025

Record is a part of a journal

• Title: Cell reports
• Publisher: Elsevier
• ISSN: 2211-1247
• COBISS.SI-ID: 27328039

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: zunajcelična past, eozinofili, glavna bazična beljakovina, metilacija DNA, tvorba por, mitohondrijske DNA, celična biologija, molekularna biologija