Glycolytic ATP production enables rapid cell growth

Abstract

Cells use ATP to fuel growth and maintenance. Surprisingly, much of the ATP in rapidly growing cells is produced through glycolytic fermentation rather than the more efficient process of respiration, a puzzling phenomenon known as the Warburg Effect. One proposed explanation is that glycolysis produces ATP faster than respiration, thereby enabling faster growth rates. But whether this explains the Warburg Effect is uncertain, as the ATP costs of mammalian cell growth have not been rigorously estimated. Here, we perform over 7500 measurements to estimate the ATP costs of growth and maintenance in mammalian cells across a range of growth rates and under perturbations to ATP production and demand. We find that respiration alone cannot meet the ATP demands of cells doubling faster than every 30 hours, roughly one-third of the maximal mammalian cell growth rate, demonstrating that the Warburg Effect is required to sustain the ATP demands of rapid cell growth.