Regulation of intracellular energy supplies by cell cycle kinetics using a single cell approach

Adenosine triphosphate (ATP) is the main energy provider for intracellular processes, through its cleavage into adenosine diphosphate (ADP) and hydrogen phosphate. The ATP/ADP ratio reflects the energy status of a cell. It is generally assumed that a high intracellular ATP/ADP ratio (i.e. a high energy potential) constitutes a signal for proliferation. Conversely, energy depletion leads to cell death. However, the consequences of cell cycle progression on cell energy consumption are unknown. Here, we quantified the ATP/ADP ratio in live cells using a single cell approach. We thus characterize a reproducible pattern of variation of the energy level throughout the cell cycle, notably with a post-mitotic decrease in the ATP/ADP ratio. In addition, the cellular energy status can be controlled by inhibiting or stimulating cell proliferation. Finally, we show that proliferating cells are more sensitive to an aggression than non-proliferating ones. Our results establish that the proliferation rate critically impacts the cellular energy state, with major implications for the pathophysiology of organ injury.