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

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

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.

• Jezik: Angleški jezik
• Ključne besede: extracellular trap, eosinophils, major basic protein, DNA methylation, mitochondrial DNA, poreformation
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 23 str.
• Številčenje: Vol. 44, iss. 4, [article no.] 114084
• PID: 20.500.12556/RUL-175845
• UDK: 576.3+577.2
• ISSN pri članku: 2211-1247
• DOI: 10.1016/j.celrep.2024.114084
• COBISS.SI-ID: 248366339
• Datum objave v RUL: 11.11.2025

Gradivo je del revije

• Naslov: Cell reports
• Založnik: Elsevier
• ISSN: 2211-1247
• COBISS.SI-ID: 27328039

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: zunajcelična past, eozinofili, glavna bazična beljakovina, metilacija DNA, tvorba por, mitohondrijske DNA, celična biologija, molekularna biologija