When cell death goes wrong: inflammatory outcomes of failed apoptosis and mitotic cell death
Florian J Bock1, Joel S Riley2
1Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands. f.bock@maastrichtuniversity.nl.
Abstract:
Apoptosis is a regulated cellular pathway that ensures that a cell dies in a structured fashion to prevent negative consequences for the tissue or the organism. Dysfunctional apoptosis is a hallmark of numerous pathologies, and treatments for various diseases are successful based on the induction of apoptosis. Under homeostatic conditions, apoptosis is a non-inflammatory event, as the activation of caspases ensures that inflammatory pathways are disabled. However, there is an increasing understanding that under specific conditions, such as caspase inhibition, apoptosis and the apoptotic machinery can be re-wired into a process which is inflammatory. In this review we discuss how the death receptor and mitochondrial pathways of apoptosis can activate inflammation. Furthermore, we will highlight how cell death due to mitotic stress might be a special case when it comes to cell death and the induction of inflammation.
Insights
Apoptosis, a programmed cell death, is usually non-inflammatory. However, this review explores how apoptosis can trigger inflammation, especially when caspases are inhibited or during mitotic stress.
Area of Science:
- Cellular Biology
- Immunology
- Pathophysiology
Background:
- Apoptosis is a crucial regulated cellular process for tissue homeostasis.
- Dysfunctional apoptosis is implicated in various diseases.
- Normally, apoptosis is non-inflammatory due to caspase activity suppressing inflammatory pathways.
Purpose of the Study:
- To review the mechanisms by which apoptosis can activate inflammatory responses.
- To discuss the role of death receptor and mitochondrial apoptosis pathways in inflammation.
- To explore cell death induced by mitotic stress as a distinct inflammatory pathway.
Main Methods:
- Literature review of apoptosis pathways and inflammation.
- Analysis of molecular mechanisms linking apoptosis to inflammation.
- Discussion of specific conditions like caspase inhibition and mitotic stress.
Main Results:
- Apoptosis, typically non-inflammatory, can become inflammatory under certain conditions, such as caspase inhibition.
- Both death receptor and mitochondrial apoptosis pathways can be re-wired to activate inflammation.
- Cell death resulting from mitotic stress presents a unique scenario for inflammation induction.
Conclusions:
- The apoptotic machinery, while usually preventing inflammation, can paradoxically drive inflammatory processes.
- Understanding these inflammatory triggers of apoptosis is vital for developing new therapeutic strategies.
- Further research into mitotic stress-induced cell death is needed to clarify its inflammatory potential.
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