Involvement of the peptide sensitive channel in the translocation of basic peptides into mitochondria.
The Peptide Sensitive Channel (PSC), a cationic channel of the mitochondrial outer membrane, is blocked by several highly basic peptides. Among these peptides, the most active are pCOX IV (1-12)Y, a mitochondrial addressing peptide and dynorphin B (1-13), a peptide unrelated to mitochondrial physiology. The voltage-dependent characteristics of the block duration of the PSC induced by these peptides and the fact that these peptides are imported into mitochondria in an in vitro assay suggest the involvement of the PSC in peptide translocation into mitochondria. We have analyzed the interaction of Mast Cell Degranulating peptide (MCD), a disulfide rich basic peptide, with yeast and mammalian mitochondria. Electrophysiological experiments with native and reduced forms of this peptide (nMCD and rMCD) showed an interaction of both forms with the yeast PSC. On the other hand, only rMCD blocked the electrical activity of the bovine adrenal cortex PSC. Similarly, although both forms inhibited the import of dynorphin B (1-13) into yeast mitochondria, only rMCD inhibited this import in bovine mitochondria. The correlation between electrophysiological and biochemical data strongly suggest that dynorphin B is translocated across the outer membrane at the level of the PSC.
Juin
P
P
Service de Neurobiologie Physico-Chimique, CNRS URA 1112, Paris, France.
Pelleschi
M
M
Sagné
C
C
Henry
J P
JP
Thieffry
M
M
Vallette
F M
FM
D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004220:Disulfides / Q000737:chemistry; D004229:Dithiothreitol; D004399:Dynorphins / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*
D004220:Disulfides; D007473:Ion Channels; D010446:Peptide Fragments; D010455:Peptides; D011994:Recombinant Proteins; C092588:dynorphin B (1-13); C093986:peptide sensitive channel; C008331:mast cell degranulating peptide; D004399:Dynorphins; D004229:Dithiothreitol