Cell death by mitotic catastrophe: a molecular definition

Castedo, Maria; Perfettini, Jean-Luc; Roumier, Thomas; Andreau, Karine; Medema, Rene; Kroemer, Guido

doi:10.1038/sj.onc.1207528

Cited by 1,269Cell death mechanisms and regulationMicrotubule and mitosis dynamicsCancer-related Molecular Pathways

Cell death by mitotic catastrophe: a molecular definition

Castedo, Maria, Perfettini, Jean-Luc, Roumier, Thomas, Andreau, Karine, Medema, Rene, Kroemer, Guido·2004·Oncogene

DOI 10.1038/sj.onc.1207528

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Abstract

The current literature is devoid of a clearcut definition of mitotic catastrophe, a type of cell death that occurs during mitosis. Here, we propose that mitotic catastrophe results from a combination of deficient cell-cycle checkpoints (in particular the DNA structure checkpoints and the spindle assembly checkpoint) and cellular damage. Failure to arrest the cell cycle before or at mitosis triggers an attempt of aberrant chromosome segregation, which culminates in the activation of the apoptotic default pathway and cellular demise. Cell death occurring during the metaphase/anaphase transition is characterized by the activation of caspase-2 (which can be activated in response to DNA damage) and/or mitochondrial membrane permeabilization with the release of cell death effectors such as apoptosis-inducing factor and the caspase-9 and-3 activator cytochrome c. Although the morphological aspect of apoptosis may be incomplete, these alterations constitute the biochemical hallmarks of apoptosis. Cells that fail to execute an apoptotic program in response to mitotic failure are likely to divide asymmetrically in the next round of cell division, with the consequent generation of aneuploid cells. This implies that disabling of the apoptotic program may actually favor chromosomal instability, through the suppression of mitotic catastrophe. Mitotic catastrophe thus may be conceived as a molecular device that prevents aneuploidization, which may participate in oncogenesis. Mitotic catastrophe is controlled by numerous molecular players, in particular, cell-cycle-specific kinases (such as the cyclin B1-dependent kinase Cdk1, polo-like kinases and Aurora kinases), cell-cycle checkpoint proteins, survivin, p53, caspases and members of the Bcl-2 family.

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Mitotic catastrophe is a regulated oncosuppressive mechanism that impedes proliferation and/or survival of cells unable to complete mitosis due to extensive DNA damage, mitotic machinery problems, and/or mitotic checkpoint failure.
“Mitotic catastrophe is a regulated oncosuppressive mechanism that impedes the proliferation and/or survival of cells that are unable to complete mitosis owing to extensive DNA damage, problems with the mitotic machinery, and/or failure of mitotic checkpoints [974, 975].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [974]

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Authors: Castedo, M., Perfettini, J.-L., Roumier, T., Andreau, K., Medema, R., & Kroemer, G.
Affiliations: Centre National de la Recherche Scientifique (FR)
Corresponding author: Kroemer, Guido
ORCID: Castedo, Maria
Perfettini, Jean-Luc
Kroemer, Guido
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2004-04-12
Volume: 23
Issue: 16
Pages: 2825-2837
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1207528
OpenAlex: W2164660906
Cited by: 1,269
References: 135
Citations by year: 2026: 25 · 2025: 34 · 2024: 28 · 2023: 59 · 2022: 57 · 2021: 57 · 2020: 52 · 2019: 49 · 2018: 58 · 2017: 59 · 2016: 64 · 2015: 45 · 2014: 72 · 2013: 78 · 2012: 64
FWCI: 4.80
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Utrecht University Repository (Utrecht University) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: mitotic catastrophe, cell death, cell cycle checkpoints, spindle assembly checkpoint, DNA damage checkpoint, caspase-2, mitochondrial membrane permeabilization, cytochrome c, apoptosis-inducing factor, aneuploidy, chromosomal instability, carcinogenesis, CDK1, Polo-like kinase, Aurora kinases, survivin, p53, Bcl-2 family proteins
MeSH terms: Animals, DNA Damage, Humans, Mitosis, Neoplasms, Polyploidy, Tumor Suppressor Protein p53, CDC2 Protein Kinase, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Cyclin B, Xenopus Proteins, Cyclin B1, Checkpoint Kinase 2

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Cell death by mitotic catastrophe: a molecular definition

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