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

Gigon, Lea; Müller, Philipp; Haenni, Beat; Iacovache, Ioan; Barbo, Maruša; Gosheva, Gordana; Yousefi, Shida; Soragni, Alice; von Ballmoos, Christoph; Zuber, Benoît; Simon, Hans-Uwe (2024). Membrane damage by MBP-1 is mediated by pore formation and amplified by mtDNA. Cell reports, 43(4), p. 114084. Cell Press 10.1016/j.celrep.2024.114084

1-s2.0-S2211124724004121-main.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (5MB) | Preview

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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Gigon, Lea, Müller, Philipp Isaak, Haenni, Beat, Iacovache, Mircea Ioan, Gosheva, Gordana, Yousefi, Shida, von Ballmoos, Christoph, Zuber, Benoît, Simon, Hans-Uwe


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry




Cell Press




Pubmed Import

Date Deposited:

08 Apr 2024 10:16

Last Modified:

27 Apr 2024 00:16

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

CP: Cell biology CP: Molecular biology DNA methylation eosinophils extracellular trap major basic protein mitochondrial DNA pore formation




Actions (login required)

Edit item Edit item
Provide Feedback