The expression of the ATPase gene (PMA1) is regulated by glucose (Rao, R., Drummond-Barbosa, D., and Slayman, C. W. (1993) Yeast 9, 1075-1084) and by the TUF/RAP1/GRF1 transcription factor (Capieaux, E., Vignais, M.-L., Sentenac, A., and Goffeau, A. (1989) J. Biol. Chem. 264, 7437-7446). In this work, we describe the isolation of mutations on seven genes that affect the levels of ATPase. One of these genes (APA1) was cloned by complementation and shown to encode a protein with six putative transmembrane stretches. Expression of APA1 gene is regulated by the carbon source and requires the protein GCR1. Deletion of APA1 causes a defective regulation of the PMA1 expression by glucose but has not noticeable effect on the expression of other TUF-regulated genes. Nevertheless the expression of glucose-repressible HXT3 and SNF3 genes is significantly reduced. These results suggest a model in which APA1 acts on a glucose-signaling pathway that controls the expression of several genes that are transcriptionally regulated by glucose.