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Updated: Jun 16, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Non-caspase proteases: triggers or amplifiers of apoptosis?
Karen Schrader1, Jisen Huai, Lars Jöckel
1Institute of Molecular Medicine and Cell Research (ZBMZ), Albert Ludwigs University Freiburg, Stefan Meier Str. 17, 79104, Freiburg, Germany.
Abstract:
Caspases are the most important effectors of apoptosis, the major form of programmed cell death (PCD) in multicellular organisms. This is best reflected by the appearance of serious development defects in mice deficient for caspase-8, -9, and -3. Meanwhile, caspase-independent PCD, mediated by other proteases or signaling components has been described in numerous publications. Although we do not doubt that such cell death exists, we propose that it has evolved later during evolution and is most likely not designed to execute, but to amplify and speed-up caspase-dependent cell death. This review shall provide evidence for such a concept.
Insights
Caspases are key to programmed cell death (PCD). While caspase-independent PCD exists, it likely evolved to enhance caspase-dependent cell death, not replace it.
Area of Science:
- Cell Biology
- Developmental Biology
- Biochemistry
Background:
- Caspases are crucial effectors of apoptosis, the primary form of programmed cell death (PCD).
- Deficiencies in key caspases (caspase-8, -9, -3) in mice lead to severe developmental defects, highlighting their essential role.
- Caspase-independent PCD pathways, mediated by various proteases and signaling molecules, have been documented extensively.
Purpose of the Study:
- To review the evidence supporting the role of caspase-independent PCD.
- To propose that caspase-independent PCD is a later evolutionary development.
- To argue that its primary function is to amplify and accelerate caspase-dependent cell death.
Main Methods:
- Literature review of studies on apoptosis and programmed cell death.
- Analysis of genetic models, particularly caspase-deficient mice.
- Comparative analysis of evolutionary timelines for different PCD pathways.
Main Results:
- Caspase-dependent apoptosis is fundamental for organismal development.
- Caspase-independent pathways are described but their evolutionary origin is debated.
- Evidence suggests these pathways may not be primary executioners of PCD.
Conclusions:
- Caspase-dependent cell death is the evolutionarily conserved and primary mechanism for PCD.
- Caspase-independent PCD likely evolved as a secondary mechanism.
- The main role of caspase-independent PCD is to augment and accelerate the execution of caspase-dependent cell death.
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The Intrinsic Apoptotic Pathway
The Extrinsic Apoptotic Pathway
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