Mastoparan Dissipates Mitochondrial Transmembrane Potential in the Physiological (ADP-LIKE) Range

Abstract

Abstract: Experimental studies of antimicrobial peptides as potential drugs having a pore-forming mechanism of action have attracted increasing interest for clinical applications due to their broad spectrum of activity. Here in a short report, we describe an experimental approach for testing potential drugs using rat liver mitochondria as model and pore-forming peptide mastoparan. We have used tightly coupled mitochondria and a sensitive oximetric cell to study activation of mitochondrial respiration by mastoparan and showed limited dissipation of their transmembrane potential in the presence of this peptide. Mastoparan stabilized this potential synchronously with stabilization of mitochondrial State 4 respiration rate (v₄). It was concluded that mastoparan dissipates mitochondrial transmembrane potential only in the physiological (adenosine diphosphate (ADP) -like) range. The comparison of side effects of pore-forming peptides on mitochondrial transmembrane potential may be useful for toxicity testing of new drugs.