Open AccessPermeabilization of the Mitochondrial Inner Membrane by Short Cecropin‐A–Melittin Hybrid Peptides
Author(s) -
DíazAchirica Pilar,
Prieto Susana,
Ubach Josep,
Andreu David,
Rial Eduardo,
Rivas Luis
Publication year - 1994
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1994.tb20019.x
Subject(s) - melittin , peptide , mitochondrion , inner mitochondrial membrane , membrane , cecropin , biochemistry , chemistry , inner membrane , biophysics , biology , antimicrobial peptides
A number of cecropin‐A–melittin hybrid peptides have previously been shown to be potent antibacterial agents [Andreu, D., Ubach, J., Boman, A., Wahlin, B., Wade, D., Merrifield, R. B. & Boman, H. G. (1992) FEBS Lett. 296 , 190–1941. In the present report we analyze their action on biological systems using rat liver mitochondria as a test system. We demonstrate that the longest peptide, cecropin‐A‐(1–8)‐melittin(l–18) permeabilizes the mitochondrial inner membrane allowing the movement of both charged and non‐charged solutes. Concentrations used have already been shown to be bactericidal. This effect is also demonstrated under respiring conditions where succinate oxidation is uncoupled. Shorter analogs also permeabilize mitochondria although at tenfold higher concentrations. Heparin potentiates the peptide effects at low concentrations, while at high concentration it becomes inhibitory. We propose that the cecropinmelittin analogs disrupt the mitochondrial membrane in a detergent‐like mode rather than by creating selective channels as had been previously suggested.