THE HANSENULA-POLYMORPHA PER1 GENE IS ESSENTIAL FOR PEROXISOME BIOGENESIS AND ENCODES A PEROXISOMAL MATRIX PROTEIN WITH BOTH CARBOXY-TERMINAL AND AMINO-TERMINAL TARGETING SIGNALS

We describe the cloning of the Hansenula polymorpha PER1 gene and the characterization of the gene and its product, PER1p. The gene was clon ed by functional complementation of a per1 mutant of H. polymorpha, wh ich was impaired in the import of peroxisomal matrix proteins (Pim(-) phenotype). The DNA sequence of PER1 predicts that PER1p is a polypept ide of 650 amino acids with no significant sequence similarity to othe r known proteins. PER1 expression was low but significant in wild-type H. polymorpha growing on glucose and increased during growth on any o ne of a number of substrates which induce peroxisome proliferation. PE R1p contains both a carboxy- (PTS1) and an amino-terminal (PTS2) perox isomal targeting signal which both were demonstrated to be capable of directing bacterial beta-lactamase to the organelle. In wild-type H. p olymorpha PER1p is a protein of low abundance which was demonstrated t o be localized in the peroxisomal matrix. Our results suggest that the import of PER1p into peroxisomes is a prerequisite for the import of additional matrix proteins and we suggest a regulatory function of PER 1p on peroxisomal protein import.