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Published on: January 20, 2023
Caspase-independent cell deaths
Richard A Lockshin1, Zahra Zakeri
1Department of Biological Sciences, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA. lockshin@stjohns.edu
Abstract:
A very common and the best understood of the mechanisms of physiological cell death is apoptosis, resulting from the activation, through either of two primary pathways, of site-specific proteases called caspases. There are, however, many other routes to cell death, prominently including autophagy and proteasomal degradation of critical constituents of cells. These routes are frequently seen in experimental situations in which initiator or effector caspases are inhibited or blocked through genetic means, but they are also encountered during normal physiological and pathological processes. Most frequently, autophagic or proteasomal degradation is used to eliminate massive cytoplasm of very large cells, especially post-mitotic cells, and these pathways are prominent even though caspase genes, messages, and pro-enzymes are found in the cells. These forms of cell death are fully physiological and not simply a default pathway for a defective cell; and they are distinct from necrosis. We do not yet understand the extent to which the pathways are linked, what mechanisms trigger the caspase-independent deaths, and how the choices are made.
Insights
Physiological cell death involves apoptosis and other pathways like autophagy. Understanding caspase-independent cell death mechanisms is crucial for cell biology research.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Apoptosis is a well-understood mechanism of physiological cell death, triggered by caspases.
- Alternative cell death pathways, including autophagy and proteasomal degradation, exist alongside apoptosis.
- These alternative pathways are observed even when caspases are inhibited and play roles in normal and pathological processes.
Purpose of the Study:
- To explore cell death mechanisms beyond apoptosis.
- To investigate the roles of autophagy and proteasomal degradation in physiological cell death.
- To highlight the distinct nature of these pathways from necrosis.
Main Methods:
- Review of existing literature on cell death mechanisms.
- Analysis of experimental data involving caspase inhibition.
- Observation of cell death pathways in physiological and pathological contexts.
Main Results:
- Autophagy and proteasomal degradation are significant routes for cell death, particularly for eliminating large cytoplasm in post-mitotic cells.
- These pathways are active independently of caspase activation.
- Caspase-independent cell death is a physiological process, not merely a default for defective cells.
Conclusions:
- Cell death encompasses multiple pathways, including caspase-dependent apoptosis and caspase-independent routes like autophagy and proteasomal degradation.
- These alternative pathways are integral to normal cellular functions and distinct from necrosis.
- Further research is needed to elucidate the triggers, links, and decision-making processes governing caspase-independent cell death.
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