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 cerev isiae on ethanol or acetate as sole carbon source, and its expression is su bject to glucose repression. It was previously shown that Acr1p is a membra ne protein which specifically transports succinate and fumarate. Its sugges ted function is to shuttle cytosolic succinate from the glyoxylate cycle in to the mitochondria in exchange for fumarate, an activity that is essential during gluconeogenic growth on C-2 compounds. In this study we show that A CR1 is coregulated with the genes coding for the key enzymes of the glyoxyl ate cycle and gluconeogenesis: ICL1, MLS1 and PCK1, FBP1 respectively. We d emonstrate that derepression of ACR1 is strictly dependent on the Zn(2)Cys( 6)-type transcriptional activator Cat8p. A detailed deletion analysis of th e ACR1 promoter revealed that 69% of the derepression of ACR1 is mediated b y three cis-acting elements, located between positions -679 and -569 relati ve to the translational start, which show a high degree of similarity to th e UAS/CSRE elements of PCK1, FBP1, ICL1 and MLS1. Our results, in conjuncti on with previous biochemical data, clearly identify Acr1p as an element whi ch is directly involved in gluconeogenesis, functioning as the mitochondria l carrier which links the anaplerotic reactions of the glyoxylate cycle to the TCA cycle.