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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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Emerging connectivity of programmed cell death pathways and its physiological implications.

Sammy Bedoui¹, Marco J Herold^2,3, Andreas Strasser^4,5

¹Department of Microbiology and Immunology at the Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.

Nature Reviews. Molecular Cell Biology

|September 3, 2020

Summary

Programmed cell death (PCD) pathways like apoptosis, necroptosis, and pyroptosis are crucial for health and disease. These pathways exhibit remarkable flexibility and crosstalk, especially during infections and cancer, acting as a coordinated system.

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Area of Science:

Cellular Biology
Immunology
Pathology

Background:

Programmed cell death (PCD) pathways are essential for removing damaged or infected cells, maintaining homeostasis, and defending against pathogens.
Key PCD pathways include apoptosis, necroptosis, and pyroptosis, each with distinct molecular mechanisms and inflammatory outcomes.

Purpose of the Study:

To review the mechanisms of different PCD pathways.
To describe the physiological and pathological processes involving crosstalk between PCD pathways.
To focus on the roles of PCD in infections and cancer.

Main Methods:

Literature review of genetic and biochemical studies.
Analysis of molecular and cellular processes of PCD pathways.
Examination of pathway interactions in physiological and pathological contexts.

Main Results:

PCD pathways display significant flexibility and plasticity in their molecular regulation.
Inflammatory caspases can mediate both pyroptosis and apoptosis; apoptotic stimuli can also trigger pyroptosis.
Pathway crosstalk is particularly pronounced in cellular responses to infection, while apoptosis is key in cancer prevention.

Conclusions:

The different PCD pathways can be viewed as a single, interconnected cell death system.
These pathways exhibit flexibility and can compensate for each other.
Understanding PCD crosstalk is crucial for addressing infections and cancer.