ArticleeLife2025
Overflow metabolism originates from growth optimization and cell heterogeneity.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- On the conditions for shifts in metabolic strategies.PLoS computational biology · 2026Review
- Growth-dependent tRNA Reprogramming and Codon Bias Link Translation to Metabolic State inbioRxiv : the preprint server for biology · 2026Article
- Spatial structure: shaping the ecology and evolution of microbial communities.FEMS microbiology reviews · 2026Review
- Engineered microbes to enable a circular economy for biodegradable plastics.Frontiers in microbiology · 2026Review
- Biomanufacturing Potential of Streamlined Cells.Biotechnology and bioengineering · 2025Article
- Review
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Authors and funding
1 author.
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Abstract
A classic problem in metabolism is that fast-proliferating cells use seemingly wasteful fermentation for energy biogenesis in the presence of sufficient oxygen. This counterintuitive phenomenon, known as overflow metabolism or the Warburg effect, is universal across various organisms. Despite extensive research, its origin and function remain unclear. Here, we show that overflow metabolism can be understood through growth optimization combined with cell heterogeneity. A model of optimal protein allocation, coupled with heterogeneity in enzyme catalytic rates among cells, quantitatively explains why and how cells choose between respiration and fermentation under different nutrient conditions. Our model quantitatively illustrates the growth rate dependence of fermentation flux and enzyme allocation under various perturbations and is fully validated by experimental results in
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