Snf1p/Hxk2p/Mig1p pathway regulates hexose transporters transcript levels, affecting the exponential growth and mitochondrial respiration of Saccharomyces cerevisiae

Fungal Genet Biol. 2022 Jul:161:103701. doi: 10.1016/j.fgb.2022.103701. Epub 2022 May 5.

Abstract

The Crabtree effect molecular regulation comprehension could help to improve ethanol production with biotechnological purposes and a better understanding of cancer etiology due to its similarity with the Warburg effect. Snf1p/Hxk2p/Mig1p pathway has been linked with the transcriptional regulation of the hexose transporters and phenotypes associated with the Crabtree effect. Nevertheless, direct evidence linking the genetic control of the hexose transporters with modulation of the Crabtree effect phenotypes by the Snf1p/Hxk2p/Mig1p pathway is still lacking. In this sense, we provide evidence that SNF1 and HXK2 genes deletion affects exponential growth, mitochondrial respiration, and transcript levels of hexose transporters in a glucose-dependent manner. The Vmax of the hexose transporters with the high transcript levels was correlated positively with the exponential growth and negatively with the mitochondrial respiration. HXT2 gene transcript levels were the most affected by the deletion of the SNF1/HXK2/MIG1 pathway. Deleting the orthologous genes SNF1 and HXK2 in Kluyveromyces marxianus (Crabtree negative yeast) has an opposite effect compared to Saccharomyces cerevisiae in growth and mitochondrial respiration. Overall, these results indicate that the SNF1/HXK2/MIG1 pathway regulates transcript levels of the hexose transporters, which shows an association with the exponential growth and mitochondrial respiration in a glucose-dependent manner.

Keywords: AMP-activated kinase (AMPK); Cell growth; Cell signaling; Mitochondrial metabolism; Mitochondrial respiration; Saccharomyces cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glucose / metabolism
  • Hexokinase* / genetics
  • Hexokinase* / metabolism
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • Protein Serine-Threonine Kinases*
  • Repressor Proteins* / genetics
  • Repressor Proteins* / metabolism
  • Respiration
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / metabolism

Substances

  • MIG1 protein, S cerevisiae
  • Monosaccharide Transport Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • SNF1-related protein kinases
  • HXK2 protein, S cerevisiae
  • Hexokinase
  • Protein Serine-Threonine Kinases
  • Glucose