Meaning of Mitotic Catastrophe
Mitotic catastrophe is considered a type of cell death that occurs in mitosis. It is caused by events that lead to aberrant mitosis, usually producing polyploid cells or cells with more than one nucleus (polynucleate). It occurs during or after defective cell division.
This mechanism may be associated with other cell death events: apoptosis and necrosis.
Therefore, it can be considered that the mitotic catastrophe is an oncosuppressive process and does not constitute a purely executive pathway of cell death. It is related to the following characteristics:
It is initiated by alterations in mitosis, either in the chromosomes or in the enzymatic chain that guarantees their complete and reliable separation.
- It begins in the M phase of the cell cycle, that is, in mitosis.
- It is concomitant with some level of mitotic arrest.
- It triggers cell death or senescence.
At the end of each stage of the cell cycle, a checkpoint (checkpoint) is performed, which checks whether any genetic damage that compromises the cell line can be derived from the checked cell. This verification is generally performed by proteins of the P53 family.
When the cell dies after checking these proteins, it is not considered a mitotic catastrophe as it is P53 independent. Likewise, it is not considered a catastrophe when the cell does not die or enters senescence after a mitotic error, causing cells with aneuploidies that continue their course.
Therefore, also, mitotic catastrophe may be a late response of some tumors that have mutated P53 and are therefore not sensitive to conventional apoptosis. Therefore, drugs that promote this mechanism are used to treat some cancers.
The official definition of mitotic catastrophe was proposed in 2012 by Galuzzi and his collaborators, although this process had already been reported before this work, which recommended a new nomenclature for various types of cell death.
Causes of Mitotic Catastrophe
Mitotic catastrophe is the main type of death caused by ionizing radiation, since it causes damage to DNA after replication, compromising the correct initiation of mitosis.
Also, chemotherapy drugs used in certain types of tumors, such as cisplatin and doxorubicin, cause mitotic catastrophe.
Mechanisms of cell death in mitotic catastrophes
In the absence of agents that disturb the cell nucleus and the mitotic apparatus, the cell cycle goes through several phases, which are: Interphase, subdivided into phases G1, S and G2; and Mitosis, subdivided into prophase, metaphase, anaphase, and telophase.
At the end, the production of diploid daughter cells is expected.
However, if chromosomal changes or mitotic machinery occur during mitosis, without the action of P53, the cells are paralyzed in this phase by activation of the mitotic catastrophe. So, they can take some destinations, they are:
- It dies without completing mitosis.
- It progresses to the G1 phase of the next cycle and dies in sequence, a process called mitotic slippage.
- End mitosis and enter senescence.
Cells in mitotic catastrophe are identified morphologically by nuclear changes that cause cell enlargement, multinucleation, and/or micronucleation.
Multinucleated cells come from chromosomes without condensation in agglomeration.
The micronucleates, on the other hand, come from fragmented or delayed chromosomes in anaphase that remained outside the main nuclei after telophase.
Importance of Mitotic Catastrophe
Mitotic catastrophe prevents cells with DNA damage from continuing their cycle and producing aneuploid or tetraploid cells. More than 90% of solid tumors and more than 50% of hematopoietic tumors had changes in the number of chromosomes reported.
Therefore, it seems that this process is very important in the prevention of tumors.
The change in the number of chromosomes in a cell during mitosis can occur through several mechanisms, such as failure of checkpoints, failure of cytokinesis or production of the mitotic spindle, and excessive replication.