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Updated: Feb 19, 2026

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
Published on: November 22, 2017
Involvement of autophagy in the outcome of mitotic catastrophe
Irina V Sorokina1, Tatiana V Denisenko1, Gabriela Imreh2,3
1Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 11999, Moscow, Russia.
Abstract:
Evading cell death is a major driving force for tumor progression that is one of the main problems in current cancer research. Mitotic catastrophe (MC) represents attractive platform compromising tumor resistance to current therapeutic modalities. MC appeared as onco-suppressive mechanism and is defined as a stage driving the cell to an irreversible destiny, i.e. cell death via apoptosis or necrosis. Our study highlights that MC induction in colorectal carcinoma cell lines ultimately leads to the autophagy followed by apoptosis. We show that autophagy suppression in Atg 13 knockout non-small cell lung carcinoma cells lead to the dramatic decrease of MC rate. Furthermore, mitochondria-linked anti-apoptotic proteins Mcl-1 and Bcl-xL play a crucial role in the duration of MC and a cross-talk between autophagy and apoptosis. Thus, the suppression of apoptosis by overexpression of Mcl-1 or Bcl-xL affected MC and lead to a significant induction of autophagy in HCT116 wt and HCT116 14-3-3σ-/- cells. Our data demonstrate that MC induction is a critical stage, in which a cell decides how to die, while mitochondria are responsible for the maintaining the balance between MC - autophagy - apoptosis.
Insights
Tumor cells evade death through mitotic catastrophe (MC), a process involving autophagy and apoptosis. Mitochondria regulate this balance, with proteins like Mcl-1 and Bcl-xL influencing cell fate decisions.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Tumor progression is driven by evasion of cell death, a significant challenge in cancer research.
- Mitotic catastrophe (MC) is a cell death pathway that can compromise therapeutic resistance.
- Understanding MC is crucial for developing effective cancer treatments.
Purpose of the Study:
- To investigate the role of autophagy and apoptosis in MC-induced cell death.
- To explore the function of mitochondria-linked anti-apoptotic proteins in MC.
- To elucidate the interplay between MC, autophagy, and apoptosis in cancer cells.
Main Methods:
- Induction of MC in colorectal and non-small cell lung carcinoma cell lines.
- Utilizing Atg13 knockout and Mcl-1/Bcl-xL overexpression models.
- Analyzing the rates of MC, autophagy, and apoptosis.
Main Results:
- MC induction in colorectal cancer cells triggers autophagy followed by apoptosis.
- Autophagy suppression significantly reduces MC rates in lung cancer cells.
- Mitochondria-associated proteins Mcl-1 and Bcl-xL modulate MC duration and the autophagy-apoptosis balance.
Conclusions:
- MC is a critical decision point for cell death, with mitochondria regulating the balance between MC, autophagy, and apoptosis.
- Targeting Mcl-1 and Bcl-xL may offer therapeutic strategies by influencing MC and cell death pathways.
- Autophagy plays a key role in the progression of MC-induced cell death.
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