Transcriptional control of AAC3 gene encoding mitochondrial ADP/ATP translocator in Saccharomyces cerevisiae by oxygen, heme and ROX1 factor (original) (raw)
1993, European Journal of Biochemistry
The AAC3 gene of Saccharomyces cerevisiae encodes a mitochondrial ADP/ATP translocator which is subject to oxygen repression. Evidence is presented here, that the repression of AAC3 expression is dependent upon heme and the ROXl factor. The promoter region of the AAC3 gene was isolated, sequenced, and deletion analysis was performed using ZacZ as a reporter gene to determine the cis-acting regions responsible for the regulation of AAC3 expression. The results of the deletion analysis show that the negative control of the AAC3 gene by oxygen and ROXl factor is mediated by an upstream repression sequence consisting of a T-rich segment adjacent to the consensus elements that are present in the 5' flanking regions of several other yeast genes. An additional upstream repressor site was located within the AAC3 promoter which, however, is not related either to oxygen or to ROXl factor. The data presented here delineate the main cellular factors and DNA sequences involved in the regulatory mechanism by which an essential function for anaerobic cells growth, ADPIATP translocation, is ensured. In addition, they show that the AAC3 gene belongs to the family of yeast genes including TIF51B, COX%, HEM13 and CYC7 that are negatively regulated by oxygen and heme. In Saccharomyces cerevisiae the mitochondria1 ADP/ATP translocator exists as three isozymes that are encoded by distinct nuclear genes, AACI, AAC2, and AAC3 [l-31. The reason for the existence of multiple genes encoding a protein functioning in ADP/ATP translocation across mitochondrial membrane is not apparent. Gene-disruption experiments have shown that the product of AAC2 gene is the major protein involved in ADP/ATP exchange across the mitochondrial membrane and that it is essential for oxidative phosphorylation [2-41. The disruption of the AACl or AAC3 gene did not yield a distinct phenotype, but the combination of these mutations with other nuclear mutations resulted in phenotypes indicating a vacuolar role for the AACZ product and a role in the anaerobic metabolism for the AAC3 product [3, It has been shown that AAC genes are differentially regulated to express separate isofoms under different physiologi-51.