Reversible and irreversible effects of basic peptides on the mitochondrial cationic channel.
We have previously shown that a 13-residue basic peptide, derived from the presequence of a mitochondrial precursor, blocked the cationic channel of the outer mitochondrial membrane. The properties of the blockade suggested that the peptide could go through the pore in the presence of a sufficient driving force. In an attempt to evaluate more precisely the relevance of such an interpretation, we have examined the effect on the same channel of basic peptides from 16 to 34 residues, most of which are parts of or derive from mitochondrial presequences. Two peptides were found to induce a reversible voltage-dependent blockade, the properties of which were the same as those of the blockade induced by the 13-residue peptide. The others had a similar effect, but triggered in addition a modification of the voltage gating that persisted after washing the peptide out. The modification was in turn abolished by trypsin added to the side of the channel previously exposed to the peptide. The protease acted on the bound peptide and not on the channel itself. The irreversible modification of the voltage gating, the mechanism of which remains obscure, was not specific for mitochondrial-addressing sequences.
Fèvre
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F
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif sur Yvette, Paris, France.
Henry
J P
JP
Thieffry
M
M
D000302:Adrenal Cortex / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000990:Antithrombin III / Q000737:chemistry; D002417:Cattle; D003576:Electron Transport Complex IV / Q000737:chemistry; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D009953:Ornithine-Oxo-Acid Transaminase / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000502:physiology
D007473:Ion Channels; D008051:Lipid Bilayers; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D000990:Antithrombin III; D003576:Electron Transport Complex IV; D009953:Ornithine-Oxo-Acid Transaminase