Egorshina Aleksandra Yu, Zamaraev Alexey V, Kaminskyy Vitaliy O, Radygina Tatiana V, Zhivotovsky Boris, Kopeina Gelina S
Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia.
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institute, P.O. Box 210, 171 77 Stockholm, Sweden.
Int J Mol Sci. 2022 Mar 29;23(7):3733. doi: 10.3390/ijms23073733.
Mitotic catastrophe is a defensive mechanism that promotes elimination of cells with aberrant mitosis by triggering the cell-death pathways and/or cellular senescence. Nowadays, it is known that apoptosis, autophagic cell death, and necrosis could be consequences of mitotic catastrophe. Here, we demonstrate the ability of a DNA-damaging agent, doxorubicin, at 600 nM concentration to stimulate mitotic catastrophe. We observe that the inhibition of caspase activity leads to accumulation of cells with mitotic catastrophe hallmarks in which RIP1-dependent necroptotic cell death is triggered. The suppression of autophagy by a chemical inhibitor or knockout upregulates RIP1 phosphorylation and promotes necroptotic cell death. Thus, in certain conditions mitotic catastrophe, in addition to apoptosis and autophagy, can precede necroptosis.
有丝分裂灾难是一种防御机制，通过触发细胞死亡途径和/或细胞衰老来促进消除有异常有丝分裂的细胞。如今，已知凋亡、自噬性细胞死亡和坏死可能是有丝分裂灾难的后果。在此，我们证明了浓度为600 nM的DNA损伤剂阿霉素刺激有丝分裂灾难的能力。我们观察到，半胱天冬酶活性的抑制导致具有有丝分裂灾难特征的细胞积累，其中触发了RIP1依赖性坏死性细胞死亡。化学抑制剂或基因敲除对自噬的抑制上调了RIP1磷酸化并促进坏死性细胞死亡。因此，在某些条件下，有丝分裂灾难除了凋亡和自噬外，还可先于坏死性凋亡发生。
