RELATIONSHIP BETWEEN THE PEPTIDE-SENSITIVE CHANNEL AND THE MITOCHONDRIAL OUTER-MEMBRANE PROTEIN TRANSLOCATION MACHINERY

The peptide-sensitive channel (PSC), a cationic channel of the mitocho ndrial outer membrane, is blocked by synthetic mitochondrial presequen ces and by nonmitochondrial basic peptides such as dynorphin B(1-13), Both types of peptides are imported into mitochondria. However, the im port of dynorphin B(1-13) had to be further characterized since its pr operties differed from those of the general import pathway used by mit ochondrial peptides. Cross-linking experiments with iodinated dynorphi n B(1-13) led to the labeling of TOM 40/ISP 42, a component of the pro tein import machinery of the outer membrane. Accordingly, dynorphin B( 1-13) could also be used as a presequence to direct the import of a cy tosolic protein into the mitochondria, Pretreatment of intact mitochon dria by trypsin removed components capable of discriminating between t rue mitochondrial presequences and other basic peptides active on the PSC. After proteolysis, both types of peptides appeared to cross the o uter membrane through the same pathway, Involvement of the PSC in the translocation complex was shown by immunoprecipitation of the PSC acti vity by anti-ISP 42 antibodies. Taken together, the present data reinf orce the hypothesis that the PSC is the pore responsible for the trans location of protein through the outer membrane.