Triosephosphates as Intermediates of the Crabtree Effect

Area of Science:

• Cellular metabolism
• Biochemistry
• Yeast genetics

Background:

• The Crabtree effect describes how increased glucose rapidly reduces cellular respiration in many cell types, including tumor cells.
• The precise molecular mechanisms underlying the Crabtree effect remain largely unknown.
• Previous research indicated that fructose-1,6-bisphosphate, a glycolysis intermediate, inhibits mitochondrial respiration.

Purpose of the Study:

• To investigate the role of glycolytic intermediates in the Crabtree effect using the yeast Saccharomyces cerevisiae.
• To identify specific intermediates responsible for the rapid decrease in respiration rate upon glucose addition.
• To explore the broader physiological impacts of glycolytic intermediate accumulation.

Main Methods:

• Utilized mutant yeast strains with glycolysis blocked at distinct stages to manipulate intracellular intermediate concentrations.
• Administered glucose and 2-deoxyglucose to observe rapid changes in cellular respiration rates.
• Cultured mutant yeast in galactose-containing media to assess growth and size changes.

Main Results:

• Glucose addition significantly impacted respiration in phosphoglycerate mutase-deficient (gpm1-delta) yeast more than in aldolase or phosphofructokinase mutants.
• Pre-incubation with 2-deoxyglucose abolished the glucose-induced respiration decrease in gpm1-delta cells, implicating triosephosphates.
• Incubation in galactose led to significant cell enlargement in gpm1-delta yeast, suggesting broader physiological effects beyond respiration.

Conclusions:

• Triosephosphates are identified as key intermediates mediating the Crabtree effect in yeast.
• The accumulation of triosephosphates influences yeast physiology beyond respiration, affecting cell growth and size.
• This study provides crucial insights into the regulatory mechanisms of cellular energy metabolism.