Mitochondrial targeting signal-induced conformational change and repression of the peroxisomal targeting signal of the precursor for rat liver serine: pyruvate/alanine : glyoxylate aminotransferase

In the rat liver, two mRNAs for serine:pyruvate (or alanine:glyoxylate) ami notransferase are generated from a single gene by alternative transcription initiation. The longer mRNA encodes a precursor of a mitochondrial enzyme that has a mitochondrial targeting signal at the N-terminus and is transloc ated into mitochondria. The shorter mRNA encodes a peroxisomal enzyme of ma ture size that is imported into peroxisomes. We have been interested in the mechanism of selective targeting to mitochondria of the precursor protein that also contains a peroxisomal targeting signal in the molecule. In this study, we examined the effect of the mitochondrial targeting signal on the conformation of the protein and on the function of the peroxisomal targetin g signal in the precursor molecule, The results suggest that the mitochondr ial targeting signal causes the conformation of the protein to become unfol ded and that this conformational change in turn causes repression of the pu tative peroxisomal targeting signal contained in the precursor protein.