Research Article

Lost in Transition: Startup of Glycolysis Yields Subpopulations of Nongrowing Cells

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Science  16 Jan 2014:
DOI: 10.1126/science.1245114

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Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic changes in the abundance of glucose can undergo growth arrest. We show that this failure is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. The imbalance arises largely from the fundamental design of glycolysis, making this state of glycolysis a generic risk. Cells with unbalanced glycolysis co-existed with vital cells. Spontaneous, non-genetic metabolic variability among individual cells determines which state is reached and consequently which cells survive. Transient ATP hydrolysis through futile cycling reduces the probability of reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.

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