Snf1p/Hxk2p/Mig1p pathway regulates exponential growth, mitochondrial respiration, and hexose transporters transcription in Saccharomyces cerevisiae

The Crabtree effect occurs under high-glucose concentrations and is characterized by the increase of the growth and a decrease in mitochondrial respiration of yeasts. Regulation of the Crabtree effect could enhance ethanol production with biotechnological purposes and a better understanding of the etiology of cancer due to its similitude with the Warburg effect. Nonetheless, the conclusive molecular mechanism of the Crabtree effect is still on debate. The pathway Snf1p/Hxk2p/Mig1p has been linked with the transcriptional regulation of the hexose transporters and has also been identified in the modulation of phenotypes related to the Crabtree effect. Nevertheless, it has not been directly identified the genetic regulation of the hexose transporters with modulation of the Crabtree effect phenotypes by Snf1p/Hxk2p/Mig1p pathway. In this sense, we provide evidence that the deletion of the SNF1 and HXK2 genes affects the exponential growth, mitochondrial respiration, and the transcription of hexose transporters in a glucose-dependent manner in Saccharomyces cerevisiae. The Vmax of the main hexose transporters transcribed showed a positive correlation with the exponential growth and a negative correlation with the mitochondrial respiration. Transcription of the gene HXT2 was the most affected by the deletion of the pathway SNF1/HXK2/MIG1. Deletion of the orthologous genes SNF1 and HXK2 in the Crabtree negative yeast, K. marxianus, has a differential effect in exponential growth and mitochondrial respiration in comparison with S. cerevisiae. Overall, these results indicate that the SNF1/HXK2/MIG1 pathway transcriptionally regulates the hexose transporters having an influence in the exponential growth and mitochondrial respiration in a glucose-dependent manner.