Hypoxic response, glucose signalling and lipid metabolism in the yeast Kluyveromyces lactis

The unicellular yeasts are suitable models to study the correlations between oxygen and glucose sensing/signalling and the physiological changes occurring when the environmental concentrations of these compounds are varying. Physiology of S. cerevisiae is predominantly governed by the glucose repression that inhibits gluconeogenesis and respiration, and induces glucose transport and fermentation. These changes occur independently on the presence of oxygen. Recently, integrated signaling between glucose and oxygen has been demonstrated. Other yeasts, for example the diary yeast K. lactis, are less sensitive to glucose repression and the equilibrium between respiration and fermentation is directly depending on oxygen availability. This yeast might be more useful than S. cerevisiae to study the cross-talking between glucose regulation and hypoxic response. However, data about oxygen-dependent regulation are still fragmentary in K. lactis. We have generated a deletion mutant of the hypoxic transcription factor encoding gene KlMGA2 in K. lactis and we have demonstrated that genes like KlPDC1 and KlOLE1 still maintained their hypoxic induction in the deleted strain, although their expression levels were lowered. Differently, other genes involved in lipid biosynthesis, such as KlERG1, KlATF1 and KlFAS1, completely lost their hypoxic induction in the mutant strain. Interestingly, the deletion of KlMGA2 caused many phenotypes, including reduction of growth rate, respiration and unsaturation index of fatty acid composition. The expression of the fatty acid poly-desaturases FAD2 and FAD3 depends on KlMga2. Transduction of glucose signalling in K. lactis has been extensively studied, especially as the expression of the low-affinity glucose transporter Rag1 is concerned. Also RAG1 is an hypoxic gene and the connection among glucose signalling, hypoxia and KlMga2 in the expression of this gene is under current investigation.