Effects of synthetic model peptides resembling the extension peptides of mitochondrial enzyme precursors on import of the precursors into mitochondria.
One common and characteristic feature of the extension peptides of mitochondrial enzyme precursors is the presence of repeating short stretches of uncharged amino acids linked by basic amino acids. We synthesized several model peptides having this particular feature of the extension peptides. The peptides contained arginine or lysine as a basic amino acid residue linking sequences of two to four residues of leucine and alanine. We examined the effects of the peptides on the import of the precursors of two mitochondrial enzymes, cytochrome P-450(SCC) and adrenodoxin, and found that the peptides were generally inhibitory to the import of the precursors into mitochondria. The effective concentrations of some of the inhibitory peptides were as low as a few microM. The peptides containing lysine instead of arginine had an essentially similar inhibitory effect on the import. The peptides did not inhibit the binding of pre-P450(SCC) to the surface of mitochondria. The synthetic model peptides uncoupled oxidative phosphorylation of mitochondria prepared from either rat liver or bovine adrenal cortex, and induced leakage of enzymes from the inner compartments of mitochondria. However, the synthetic model peptides did not solubilize membrane-bound enzymes from mitochondria, suggesting that their effect on the membranes is different from that of detergents. The synthetic model peptides seem to bind to the membranes causing significant perturbation in the membrane structure, which is possibly related to the functions of the particular common sequence found in the extension peptides of mitochondrial enzyme precursors.
D000325:Adrenodoxin / Q000096:biosynthesis; D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D007425:Intracellular Membranes / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010455:Peptides; D011498:Protein Precursors; D000325:Adrenodoxin; D003577:Cytochrome P-450 Enzyme System