INVOLVEMENT OF THE PEPTIDE SENSITIVE CHANNEL IN THE TRANSLOCATION OF BASIC PEPTIDES INTO MITOCHONDRIA

The Peptide Sensitive Channel (PSC), a cationic channel of the mitocho ndrial outer membrane, is blocked by several highly basic peptides. Am ong these peptides, the most active are pCOX IV (1-12)Y, a mitochondri al addressing peptide and dynorphin B (1-13), a peptide unrelated to m itochondrial 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 sug gest the involvement of the PSC in peptide translocation into mitochon dria. We have analyzed the interaction of Mast Cell Degranulating pept ide (MCD), a disulfide rich basic peptide, with yeast and mammalian mi tochondria. Electrophysiological experiments: with native and reduced forms of this peptide (nMCD and rMCD) showed an interaction of both fo rms with the yeast PSC. On the other hand, only rMCD blocked the elect rical activity of the bovine adrenal cortex PSC. Similarly, although b oth forms inhibited the import of dynorphin B (1-13) into yeast mitoch ondria, only rMCD inhibited this import in bovine mitochondria. The co rrelation between electrophysiological and biochemical data strongly s uggest that dynorphin B is translocated across the outer membrane at t he level of the PSC. (C) 1995 Academic, Press.