ATP depletion during mitotic arrest induces mitotic slippage and APC/CCdh1-dependent cyclin B1 degradation

Abstract

Cancer chemotherapy: A lack of energy overcomes cells’ stall An investigation into the effects of cellular energy depletion reveals a potential mechanism by which tumors evade chemotherapy. Adenosine triphosphate (ATP) is the primary energetic currency for many biological processes, and ATP depletion generally stalls the cell cycle that regulates proliferation. However, researchers led by Jae-Ho Lee of South Korea’s Ajou University School of Medicine discovered that ATP-depleted cells can sometimes bypass roadblocks in the cell division process. Before dividing, cells synthesize duplicates of every chromosome, and Lee’s team treated cells with chemotherapy agents that stall cell division by preventing separation of these duplicates. Surprisingly, subsequent ATP depletion allowed these cells to bypass this arrested state and re-enter the cell cycle, albeit with twice as much DNA as normal. Since many cancerous cells experience ATP depletion, this ‘escape hatch’ could help tumors survive treatment.