Peroxisome biogenesis in Saccharomyces cerevisiae.

The observation that peroxisomes of Saccharomyces cerevisiae can be induced by oleic acid has opened the possibility to investigate the biogenesis of these organelles in a biochemically and genetically well characterized organism. Only few enzymes have been identified as peroxisomal proteins in Saccharomyces cerevisiae so far; the three enzymes involved in beta-oxidation of fatty acids, enzymes of the glyoxylate cycle, catalase A and the PAS3 gene product have been unequivocally assigned to the peroxisomal compartment. However, more proteins are expected to be constituents of the peroxisomes in Saccharomyces cerevisiae. Mutagenesis of Saccharomyces cerevisiae cells gave rise to mutants unable to use oleic acid as sole carbon source. These mutants could be divided in two groups: those with defects in structural genes of beta-oxidation enzymes (fox-mutants) and those with defects in peroxisomal assembly (pas-mutants). All fox-mutants possess morphologically normal peroxisomes and can be assigned to one of three complementation groups (FOX1, 2, 3). All three FOX genes have been cloned and characterized. The pas-mutants isolated are distributed among 13 complementation groups and represent 3 different classes: peroxisomes are either morphologically not detectable (type I) or present but non-proliferating (type II). Mislocalization concerns all peroxisomal proteins in cells of these two classes. The third class of mutants contains peroxisomes normal in size and number, however, distinct peroxisomal matrix proteins are mislocalized (type III). Five additional complementation groups were found in the laboratory of H.F. Tabak. Not all PAS genes have been cloned and characterized so far, and only for few of them the function could be deduced from sequence comparisons. Proliferation of microbodies is repressed by glucose, derepressed by non-fermentable carbon sources and fully induced by oleic acid. The regulation of four genes encoding peroxisomal proteins (PAS1, CTA1, FOX2, FOX3) occurs on the transcriptional level and reflects the morphological observations: repression by glucose and induction by oleic acid. Moreover, trans-acting factors like ADR1, SNF1 and SNF4, all involved in derepression of various cellular processes, have been demonstrated to affect transcriptional regulation of genes encoding peroxisomal proteins. The peroxisomal import machinery seems to be conserved between different organisms as indicated by import of heterologous proteins into microbodies of different host cells. In addition, many peroxisomal proteins contain C-terminal targeting signals. However, more than one import route into peroxisomes does exist.(ABSTRACT TRUNCATED AT 400 WORDS)