Respiration and low cAMP-dependent protein kinase activity are required for high-level expression of the peroxisomal thiolase gene in Saccharomyces cerevisiae

Abstract

Transcription of genes for peroxisomal proteins is repressed by glucose and induced by oleate. At least for the peroxisomal thiolase gene (POT1) there is a third regulatory mechanism, mediated by the transcription factor Adr1p, which is responsible for the high-level expression of the gene in stationary phase. Here we show that a region in the POT1 promoter that extends from positions -238 to -152 mediates this mechanism, and we suggest that Adr1p acts indirectly on POT1. We have also analyzed the role of the cAMP-dependent protein kinase (PKA) in the transcriptional regulation of POT1. PKA exerts a negative control: the high, unregulated PKA activity in a bcy1 mutant maintains POT1 transcription at the repressed level. In a ras2 mutant, which has low PKA activity, glucose repression is not alleviated but in non-repressing conditions POT1 regulation is perturbed and expression prematurely increases during exponential phase. This suggests that the PKA signalling pathway controls the regulation of POT1 in stationary phase. Finally, we have found that Adr1p-dependent expression in stationary phase and induction by oleate are both abolished when respiration is blocked. Utilization of fatty acids as carbon source requires respiration. Our result points to the existence of mechanisms that co-ordinate the level of expression of thiolase and the functional state of the mitochondria.