Characterization and function of the mitochondrial outer membrane peptide-sensitive channel.
The PSC (peptide-sensitive Channel), a cationic channel of large conductance, has been characterized in yeast and mammalian mitochondria by three different methods, "tip-dip," patch clamp of giant liposomes, and planar bilayers. The yeast and mammalian PSC share the common property to be blocked by basic peptides such as pCyt OX IV (1-12)Y which contains the first 12 residues of the presequence of cytochrome C oxidase subunit IV. The electrophysiological data are consistent with a translocation of the peptide through the pore. Analysis of the frequency of observation of the PSC in different fractions indicates that the channel is located in the outer mitochondrial membrane. Uptake measurements of iodinated peptides by intact mitochondria from a porin-less mutant show that the peptides are translocated through the outer membrane, presumably at the level of PSC. Among the peptides active on PSC, several, such as pCyt OX IV (1-22) and the reduced form of the mast cell degranulating peptide, induce an alteration of the voltage dependence or of the inactivation rate subsisting after washing and which is eliminated only by proteolysis of the interacting peptide. These irreversible effects may account for the variability of the properties of the PSC which would interact with cytosolic or intermembrane cations, peptides, or proteins, thus modulating the channel permeability. Finally, several lines of evidence suggest the participation of the PSC in protein translocation and some interaction with the general insertion pore of the outer membrane translocation machinery.
Henry
J P
JP
Centre National de la Recherche Scientifique, Service de Neurobiologie Physico-Chimique, Institut de Biologie Physico-Chimique, Paris, France.
Juin
P
P
Vallette
F
F
Thieffry
M
M
D000595:Amino Acid Sequence; D000818:Animals; D004594:Electrophysiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D007473:Ion Channels; D010455:Peptides; D011506:Proteins; C093986:peptide sensitive channel