Accumulation of human promyelocytic leukemic (HL-60) cells at two energetic cell cycle checkpoints.

Agents that disrupt mitochondrial function were used to monitor the contribution of ATP to cell cycle progression. Following nontoxic exposure to these agents, flow cytometric analysis of the cell population showed a significant increase in the proportion of cells in G1 at low doses of the agent and in G2-M at higher doses, in accordance with the degree of ATP reduction induced by the compound. These data indicate that cycling cells must maintain a minimal ATP content to satisfy the energy requirement of the checkpoint that allows passage through G1 into S phase. Once committed, successful passage through G2 into mitosis is also conditional upon maintenance of a critical ATP content sufficient to satisfy the second energy-sensitive checkpoint that exists at this transition. These data establish a foundation for future investigations into the energy dependence of cell cycle events and propose novel means for cell cycle intervention.