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Updated: Mar 26, 2026
Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae
Published on: April 5, 2015
Screening the yeast genome for energetic metabolism pathways involved in a phenotypic response to the anti-cancer
Paweł Lis1, Paweł Jurkiewicz1, Magdalena Cal-Bąkowska1
1Department of Genetics, Institute of Genetics and Microbiology, University of Wrocław, Wrocław, Poland.
Abstract:
In this study the detailed characteristic of the anti-cancer agent 3-bromopyruvate (3-BP) activity in the yeast Saccharomyces cerevisiae model is described, with the emphasis on its influence on energetic metabolism of the cell. It shows that 3-BP toxicity in yeast is strain-dependent and influenced by the glucose-repression system. Its toxic effect is mainly due to the rapid depletion of intracellular ATP. Moreover, lack of the Whi2p phosphatase results in strongly increased sensitivity of yeast cells to 3-BP, possibly due to the non-functional system of mitophagy of damaged mitochondria through the Ras-cAMP-PKA pathway. Single deletions of genes encoding glycolytic enzymes, the TCA cycle enzymes and mitochondrial carriers result in multiple effects after 3-BP treatment. However, it can be concluded that activity of the pentose phosphate pathway is necessary to prevent the toxicity of 3-BP, probably due to the fact that large amounts of NADPH are produced by this pathway, ensuring the reducing force needed for glutathione reduction, crucial to cope with the oxidative stress. Moreover, single deletions of genes encoding the TCA cycle enzymes and mitochondrial carriers generally cause sensitivity to 3-BP, while totally inactive mitochondrial respiration in the rho0 mutant resulted in increased resistance to 3-BP.
Insights
The anti-cancer agent 3-bromopyruvate (3-BP) affects yeast energetic metabolism, with toxicity depending on glucose repression and strain. The pentose phosphate pathway is crucial for preventing 3-BP toxicity by producing NADPH.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Engineering
Background:
- The anti-cancer agent 3-bromopyruvate (3-BP) is known to affect cellular energy metabolism.
- Understanding its precise mechanisms in a model organism is crucial for further therapeutic development.
Purpose of the Study:
- To characterize the anti-cancer agent 3-bromopyruvate (3-BP) activity in Saccharomyces cerevisiae.
- To investigate the influence of 3-BP on cellular energetic metabolism and identify factors affecting its toxicity.
Main Methods:
- Yeast (Saccharomyces cerevisiae) strains with gene deletions in metabolic pathways were used.
- Cellular ATP levels, oxidative stress response, and sensitivity to 3-BP were analyzed.
- The role of the Ras-cAMP-PKA pathway and mitophagy was investigated.
Main Results:
- 3-BP toxicity is strain-dependent and influenced by glucose repression, primarily causing rapid ATP depletion.
- Loss of Whi2p phosphatase increases sensitivity to 3-BP, potentially via impaired mitophagy.
- The pentose phosphate pathway is essential for preventing 3-BP toxicity by supplying NADPH for oxidative stress management.
Conclusions:
- 3-BP's anti-cancer activity is linked to its disruption of cellular energy metabolism.
- The pentose phosphate pathway plays a protective role against 3-BP-induced toxicity.
- Mitochondrial function and specific metabolic pathways significantly modulate yeast sensitivity to 3-BP.
