Transcriptional regulation of the KlDLD gene, encoding the mitochondrial enzyme D-lactate ferricytochrome c oxidoreductase in Kluyveromyces lactis: effect of Klhap2 and fog mutations.

Expression of the Kluyveromyces lactis KlDLD gene, encoding the mitochondrial enzyme D-lactate ferricytochrome c oxidoreductase (D-LCR), is subject to two metabolic controls at the transcriptional level: induction by lactate, the substrate of the D-LCR enzyme, and repression by glucose. By Northern analysis we determined the kinetics of the two regulatory processes and, by measurement of the expression of LacZ gene fused to the KlDLD promoter, we identified cis-elements involved in glucose repression and lactate induction. The effect of trans-acting factors on the transcription of KlDLD has been analyzed. The KlDLD gene is controlled by the products of the FOG1 and FOG2 genes, previously identified as involved in glucose de-repression. Moreover, the KlDLD gene is regulated by the product of KlHAP2, homologous to the HAP2 gene which in Saccharomyces cerevisiae is required for the induction of genes encoding mitochondrial components, upon shifting from a fermentable to a non-fermentable carbon source. We have demonstated that the KlHAP2 gene is necessary both for the lactate induction of KlDLD mRNA synthesis and for growth on this oxidative carbon source.