Mitochondria permeabilization by a novel polycation peptide BTM-P1

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Bacillus thuringiensis subsp. medellin produces the Cry11Bb protein, toxic to mosquito larvae via midgut epithelial cell membrane permeabilization.
• A synthetic peptide, BTM-P1, derived from Cry11Bb, exhibits activity against bacteria.

Purpose of the Study:

• To investigate the effects of the BTM-P1 peptide on rat liver mitochondria.
• To elucidate the mechanism of BTM-P1-induced mitochondrial membrane permeabilization.

Main Methods:

• Mitochondrial swelling assays in various salt solutions.
• Measurement of mitochondrial inner membrane potential.
• Assessment of oxidative phosphorylation uncoupling.
• Analysis of peptide effects with varying ionic conditions and energization.

Main Results:

• BTM-P1 induced cyclosporin A-insensitive mitochondrial swelling, potentiated by phosphate and Ca(2+).
• The peptide uncoupled oxidative phosphorylation, decreasing inner membrane potential, particularly in potassium-containing media.
• Mitochondrial effects were dependent on specific ions and peptide modifications (N-terminal tryptophan).

Conclusions:

• BTM-P1 induces mitochondrial membrane permeabilization through a mechanism involving peptide insertion, oligomerization, and ion channel formation.
• The process is independent of the cyclosporin A-sensitive pathway and influenced by membrane potential and ionic environment.
• N-terminal modification abolishes the peptide's mitochondrial activity, suggesting its critical role in the interaction.