<scp> <i>PDC1</i> </scp> deficiency results in 2‐deoxyglucose sensitivity through inhibition of Pdc2 activity in yeast

Pyruvate decarboxylase (PDC) catalyzes the decarboxylation of pyruvate to yield acetaldehyde, using thiamine pyrophosphate as a coenzyme. Saccharomyces cerevisiae has two functional PDCs, Pdc1 and Pdc5, whose reactions constitute the first step in the alcoholic fermentation pathway. PDC1 is abundantly expressed in wild-type cells, whereas PDC5 is markedly repressed when cells are cultured in a glucose medium. PDC5 expression is induced in a Pdc1 deletion mutant, a phenomenon referred to as autoregulation, and this induction depends on the transcriptional regulator Pdc2. Therefore, it has been proposed that Pdc1 plays a role as a regulator of gene expression, in addition to its function as a PDC. However, the regulatory mechanism by which Pdc1 represses the PDC5 induction remains poorly understood. In addition, the phenotypes resulting from PDC1 deficiency alone are poorly understood because PDC5 expression, through autoregulation, compensates for the overall PDC activity in the cell. Here, we showed that a PDC1 deletion mutant exhibited increased sensitivity to 2-deoxyglucose (2-DG). We found that overexpression of PDC2 suppressed the 2-DG-sensitive phenotype of pdc1∆ cells and that 2-DG decreased cellular PDC activity through inhibiting Pdc2. The suppressive effect of Pdc2 was abolished by truncation of an intrinsically disordered region at its C terminus. The increased sensitivity to 2-DG may be useful for understanding the mechanism by which Pdc1 regulates PDC5 expression via Pdc2.