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Mitotic progression and ATP depletion

Park, Yun-Yeon; Lee, In-Jeong; Lee, Jae-Ho
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine
The control of the progression along the cell cycle ultimately consists in the activation of kinase which phosphorylates substrates using ATP as the donor of high-energy phosphoryl groups. It has been shown that tumor cells possess two main energy checkpoints monitoring the amount of available ATP during G1 phase and their progression from G2 to M phase. However, it is still uncertain the energy dependency during mitotic progression. In our study, co-treatment with 2-deoxy glucose and sodium azide reduced intracellular ATP level as low as ATP level of asynchronous cells. When ATP was depleted, cells in interphase stopped their cell cycle and stayed at the moment following complete blockage of mitotic entry. On the other hand, reduction of ATP did not affect mitotic exit. Interestingly, mitotic cells in the existence of activated spindle assembly checkpoint were reactive to ATP depletion resulting in mitotic slippage which was confirmed by cyclin B degradation, increase of cell attachment, and reassembly of nuclear membrane. Taken together, cells showed different energy dependency between mitotic entry and mitotic exit. In activation of spindle assembly checkpoint, ATP deletion of mitotic cells induced mitotic slippage.
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