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Circumventing the Crabtree effect in cell culture: A systematic review
Michèle J C de Kok1, Alexander F Schaapherder1, Rob C I Wüst2
1Department of Surgery and Leiden Transplant Center, Leiden University Medical Center, Leiden, The Netherlands.
Mitochondrion
|April 4, 2021
Summary
The Crabtree effect, where cells favor glycolysis over oxidative phosphorylation in culture, can skew metabolic research. This review critically appraises strategies to overcome this common cell culture artifact.
Area of Science:
- Cellular metabolism
- Mitochondrial function
- Biomedical research techniques
Background:
- Metabolic reprogramming and mitochondrial dysfunction are crucial in physiology and pathology.
- Standard cell culture methods are often compromised by the Crabtree effect, where cultured cells exhibit a glycolytic phenotype.
- This phenomenon challenges the validity of cell culture models for studying cellular metabolism.
Purpose of the Study:
- To provide a comprehensive overview of strategies to circumvent the Crabtree effect.
- To critically appraise existing methods for overcoming metabolic artifacts in cell culture.
- To enhance the reliability of cell-based studies on metabolism.
Main Methods:
- Systematic literature review.
- Critical appraisal of published methodologies.
- Analysis of strategies to mitigate the Crabtree effect in cell culture.
Main Results:
- Identified and categorized various strategies to overcome the Crabtree effect.
- Evaluated the efficacy and limitations of each strategy.
- Highlighted the impact of the Crabtree effect on metabolic research.
Conclusions:
- The Crabtree effect is a significant challenge in cell culture-based metabolic studies.
- Several strategies can mitigate or circumvent the Crabtree effect.
- Careful consideration of experimental design is essential for accurate metabolic research in vitro.

