CONVERSION OF A NONPROCESSED MITOCHONDRIAL PRECURSOR PROTEIN INTO ONETHAT IS PROCESSED BY THE MITOCHONDRIAL PROCESSING PEPTIDASE

Mitochondrial processing peptidase (MPP) cleaves the signal sequence f rom a variety of mitochondrial pre cursor proteins. A subset of mitoch ondrial proteins, including rhodanese and 3-oxoacyl-CoA thiolase, are imported into the matrix space, yet are not processed. Rhodanese signa l peptide and translated protein were recognized by MPP, as both were inhibitors of processing. The signal peptide of precursor aldehyde deh ydrogenase consists of a helix-linker helix motif but when the RGP lin ker is removed, processing no longer occurs (Thornton, K., Wang, Y., W einer, H., and Gorenstein, D. G. (1993) J. Biol. Chem. 268, 19906-1991 4). Disruption of the helical signal sequence of rhodanese by the addi tion of the RGP linker did not allow cleavage to occur. However, addit ion of a putative cleavage site allowed the protein to be processed. T he same cleavage site was added to 3-oxoacyl-CoA thiolase, but this pr otein was still not processed, Thiolase and linker-deleted aldehyde de hydrogenase signal peptides were poor inhibitors of MPP. It can be con cluded that both a processing site and the structure surrounding this site are important for MPP recognition.