The succinate/fumarate transporter Acr1p of Saccharomyces cerevisiae is part of the gluconeogenic pathway and its expression is regulated by Cat8p.
The product of the ACR1 gene is essential for growth of Saccharomyces cerevisiae on ethanol or acetate as sole carbon source, and its expression is subject to glucose repression. It was previously shown that Acr1p is a membrane protein which specifically transports succinate and fumarate. Its suggested function is to shuttle cytosolic succinate from the glyoxylate cycle into the mitochondria in exchange for fumarate, an activity that is essential during gluconeogenic growth on C2 compounds. In this study we show that ACR1 is coregulated with the genes coding for the key enzymes of the glyoxylate cycle and gluconeogenesis: ICL1, MLS1 and PCK1, FBP1 respectively. We demonstrate that derepression of ACR1 is strictly dependent on the Zn2Cys6-type transcriptional activator Cat8p. A detailed deletion analysis of the ACR1 promoter revealed that 69% of the derepression of ACR1 is mediated by three cis-acting elements, located between positions -679 and -569 relative to the translational start, which show a high degree of similarity to the UAS/CSRE elements of PCK1, FBP1, ICL1 and MLS1. Our results, in conjunction with previous biochemical data, clearly identify Acr1p as an element which is directly involved in gluconeogenesis, functioning as the mitochondrial carrier which links the anaplerotic reactions of the glyoxylate cycle to the TCA cycle.
Bojunga
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Institut für Mikrobiologie, Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.
Kötter
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Entian
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D050976:Basic-Leucine Zipper Transcription Factors; D001692:Biological Transport; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D019802:Succinic Acid / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D050976:Basic-Leucine Zipper Transcription Factors; C092600:CAT8 protein, S cerevisiae; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C085976:MIG1 protein, S cerevisiae; D012097:Repressor Proteins; C077832:SKO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D019802:Succinic Acid; D005947:Glucose