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Updated: Feb 11, 2026
Observing Mitotic Division and Dynamics in a Live Zebrafish Embryo
Published on: July 15, 2016
ATP depletion during mitotic arrest induces mitotic slippage and APC/CCdh1-dependent cyclin B1 degradation
Yun Yeon Park1,2, Ju-Hyun Ahn1,3,4, Min-Guk Cho1,3,4
1Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, South Korea.
Abstract:
ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly. Additionally, cells successfully progressed through the cell cycle after mitotic slippage, as indicated by EdU incorporation and time-lapse imaging. Although degradation of cyclin B during normal mitotic progression is primarily regulated by APC/CCdc20, we observed an unexpected decrease in Cdc20 prior to degradation of cyclin B during mitotic slippage. This decrease in Cdc20 was followed by a change in the binding partner preference of APC/C from Cdc20 to Cdh1; consequently, APC/CCdh1, but not APC/CCdc20, facilitated cyclin B degradation following ATP depletion. Pulse-chase analysis revealed that ATP depletion significantly abrogated global translation, including the translation of Cdc20 and Cdh1. Additionally, the half-life of Cdh1 was much longer than that of Cdc20. These data suggest that ATP depletion during mitotic arrest induces mitotic slippage facilitated by APC/CCdh1-dependent cyclin B degradation, which follows a decrease in Cdc20 resulting from reduced global translation and the differences in the half-lives of the Cdc20 and Cdh1 proteins.
Insights
Adenosine triphosphate (ATP) depletion during mitotic arrest triggers mitotic slippage. This process involves APC/CCdh1-mediated cyclin B1 degradation, allowing cells to exit mitosis despite low energy levels.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Adenosine triphosphate (ATP) depletion is known to inhibit cell cycle progression at G1 and G2/M transitions.
- The precise impact of ATP depletion on mitotic progression, particularly during prometaphase arrest, remains poorly understood.
Purpose of the Study:
- To investigate the effect of ATP depletion on mitotic progression.
- To elucidate the underlying molecular mechanisms driving mitotic events under energy-depleted conditions.
Main Methods:
- Cells were treated with 2-deoxyglucose and NaN3 to deplete ATP.
- Nocodazole was used to induce prometaphase arrest.
- Mitotic slippage was assessed via cell counts, cyclin B1 degradation, cell attachment, and nuclear envelope reassembly.
- Protein translation and half-life were analyzed using pulse-chase experiments.
- The role of APC/C complexes (APC/CCdc20 and APC/CCdh1) was investigated.
Main Results:
- ATP depletion during nocodazole-induced mitotic arrest did not cause arrest but resulted in mitotic slippage.
- Mitotic slippage was characterized by decreased mitotic cells, cyclin B1 degradation, increased cell attachment, and nuclear reassembly.
- ATP depletion reduced global translation, leading to decreased Cdc20 levels.
- APC/CCdh1, not APC/CCdc20, mediated cyclin B1 degradation during slippage due to altered APC/C binding partners.
- Cdh1 exhibited a longer half-life than Cdc20 under ATP-depleted conditions.
Conclusions:
- ATP depletion during mitotic arrest induces mitotic slippage.
- Mitotic slippage is facilitated by APC/CCdh1-dependent cyclin B1 degradation.
- Reduced global translation and differential protein half-lives of Cdc20 and Cdh1 contribute to the shift in APC/C activity.
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