Related Experiment Video

Updated: Jun 29, 2025

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

2.3K

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

Lea Gigon1, Philipp Müller2, Beat Haenni3

  • 1Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland.

Cell Reports
|April 7, 2024
PubMed

Insights

Major basic protein 1 (MBP-1) forms pores in cell membranes, disrupting potassium balance. Mitochondrial DNA (mtDNA) in eosinophil extracellular traps (EETs) enhances MBP-1 toxicity, with unmethylated CpG sites potentially regulating this effect.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Eosinophils are key immune cells involved in host defense and immunopathology.
  • They release cytotoxic proteins, including major basic protein 1 (MBP-1), from granules.
  • The precise mechanism of MBP-1 toxicity and its regulation are not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of MBP-1-induced membrane damage.
  • To investigate the role of mitochondrial DNA (mtDNA) in eosinophil extracellular traps (EETs) in modulating MBP-1 toxicity.
  • To explore the potential regulatory role of CpG methylation in mtDNA on MBP-1-mediated effects.

Main Methods:

  • Lipid bilayer assays to assess membrane permeabilization by MBP-1.
  • Potassium flux measurements to evaluate ion balance disruption.
  • Analysis of MBP-1 toxicity in the presence and absence of mtDNA within EETs.
  • Investigation of CpG methylation status in mtDNA.

Main Results:

  • MBP-1 forms pores in lipid bilayers, leading to membrane permeabilization and potassium imbalance.
  • Mitochondrial DNA (mtDNA) within eosinophil extracellular traps (EETs) significantly amplifies MBP-1's toxic effects.
  • Absence of CpG methylation in mtDNA appears to contribute to the regulation of MBP-1-mediated toxicity.

Conclusions:

  • MBP-1 induces cellular damage by creating pores and disrupting ion homeostasis.
  • The mtDNA scaffold within EETs plays a critical role in potentiating MBP-1 toxicity.
  • CpG methylation status of mtDNA may serve as a regulatory mechanism for MBP-1-induced immunopathology.
Keywords:
CP: Cell biologyCP: Molecular biologyDNA methylationeosinophilsextracellular trapmajor basic proteinmitochondrial DNApore formation

More Related Videos

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

10.8K
Cell Membrane Repair Assay Using a Two-photon Laser Microscope06:35

Cell Membrane Repair Assay Using a Two-photon Laser Microscope

Published on: January 2, 2018

12.4K

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.0K
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.0K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K