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Triosephosphates as Intermediates of the Crabtree Effect
S S Sokolov1, O V Markova, K D Nikolaeva
1Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow, 119991, Russia. severin@belozersky.msu.ru.
Biochemistry. Biokhimiia
|April 4, 2017
Summary
Triosephosphates, key molecules in sugar breakdown, appear to drive the Crabtree effect, a phenomenon where glucose lowers cell respiration. This finding sheds light on cellular energy regulation in yeast.
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.