The Crabtree and Warburg effects both involve elevated glycolytic flux and fermentation under aerobic conditions, yet their regulatory bases differ fundamentally. In the Crabtree effect, high-glucose concentrations suppress mitochondrial respiration, redirecting carbon flux toward fermentation. In contrast, the Warburg effect, characteristic of many cancer cells, features increased mitochondrial respiration to support biosynthetic and anaplerotic demands. We recently advanced an extended metabolic definition of the Warburg effect that incorporates enhanced amino acid catabolism and elevated lipid biosynthesis, reflecting broad mitochondrial engagement beyond oxidative phosphorylation. Revisiting the metabolic behavior of the snf1∆ strain of Saccharomyces cerevisiae, which lacks the Crabtree effect, reveals a phenotype analogous to this expanded Warburg effect framework. Under glucose-rich conditions that typically elicit the Crabtree effect, snf1∆ cells preserve high mitochondrial respiration while maintaining robust glycolysis and fermentation. These cells also display enhanced amino acid degradation that feeds the Krebs cycle and increased lipid synthesis, recapitulating hallmark features of the Warburg state. Notably, mutation of the AMPK gene, the human ortholog of SNF1, similarly drives Warburg-like reprogramming in mammalian models. Together, these data establish snf1∆ as a valuable eukaryotic model for dissecting the regulatory determinants of the Warburg effect.
Nava et al. (Wed,) studied this question.