Effects of amphipathic peptides, including presequences, on the functional integrity of rat liver mitochondrial membranes.
A number of amphipathic peptides were tested for their effects on structural and functional properties of isolated rat liver mitochondria. The peptides included the matrix targeting sequence of subunit IV of (yeast) cytochrome c oxidase. Titration experiments in which the mitochondria were incubated with increasing concentrations of the peptides revealed two major stages in the interaction. First, at low peptide/mitochondria ratios, peptide binding to the outer membrane occurred which was accompanied by gradual lysis of the outer membrane at higher ratios. The latter was deduced from the release of adenylate kinase, the classical marker enzyme of the intermembrane space. Secondly, at still higher peptide/mitochondria ratios, the permeability of the inner membrane progressively increased, as evidenced by measurements of respiratory control and of the membrane potential. Complete uncoupling of respiration seemed to precede dissipation of the membrane potential.
Nicolay
K
K
Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands.
Laterveer
F D
FD
van Heerde
W L
WL
D000263:Adenylate Kinase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007425:Intracellular Membranes / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides; D051381:Rats; D017208:Rats, Wistar; D014862:Wasp Venoms / Q000494:pharmacology*
D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan; D003576:Electron Transport Complex IV; D000263:Adenylate Kinase