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Updated: Aug 21, 2026
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Life's smile, death's grin: vital functions of apoptosis-executing proteins
Carmen Garrido1, Guido Kroemer
1INSERM U-517, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21033 Dijon, France. cgarrido@u-bourgogne.fr
Abstract:
Apoptosis is executed by caspases as well as caspase-independent death effectors. Caspases are expressed as inactive zymogens in virtually all animal cells and are activated in cells destined to undergo apoptosis. However, there are many examples where caspase activation is actually required for cellular processes not related to cell death, namely terminal differentiation, activation, proliferation, and cytoprotection. Several caspase-independent death effectors including apoptosis-inducing factor, endonuclease G and a serine protease (Omi/HtrA2) are released from the mitochondrial intermembrane space upon permeabilization of the outer membrane. Such proteins also have important roles in cellular redox metabolism and/or mitochondrial biogenesis. As a general rule, it thus appears that cell-death-relevant proteins, especially those involved in the core of the executing machinery, have a dual function in life and death. This has important implications for pathophysiology. The fact that the building blocks of the apoptotic machinery have normal functions not related to cell death may mean that essential parts of the apoptotic executioner cannot be lost and thus reduces the possibility of oncogenic mutations that block the apoptotic program. Moreover, therapeutic suppression of unwarranted cell death must be designed to target only the lethal (and not the vital) role of death effectors.
Insights
Cell death proteins, like caspases, have dual roles in both life and death processes. Understanding these functions is crucial for developing targeted therapies for diseases involving cell death.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis, or programmed cell death, is primarily executed by caspases and caspase-independent pathways.
- Caspases, initially inactive zymogens, are activated during apoptosis but also play roles in non-lethal cellular functions like differentiation and proliferation.
- Caspase-independent death factors, such as apoptosis-inducing factor and endonuclease G, are released from mitochondria and involved in vital cellular processes.
Purpose of the Study:
- To explore the dual functions of cell death machinery components in both life and death processes.
- To investigate the implications of these dual roles in pathophysiology and therapeutic strategies.
Main Methods:
- Review and synthesis of existing literature on apoptosis executioners.
- Analysis of the roles of caspases and caspase-independent factors in cellular processes.
- Examination of the pathophysiological relevance of these dual functions.
Main Results:
- Proteins involved in apoptosis execution, including caspases and mitochondrial death effectors, possess essential functions unrelated to cell death.
- These proteins are involved in critical cellular activities such as differentiation, proliferation, cytoprotection, redox metabolism, and mitochondrial biogenesis.
- The dual roles suggest that core apoptotic machinery components are evolutionarily conserved, limiting oncogenic mutations that abolish cell death.
Conclusions:
- Cell death effectors have vital physiological roles, indicating a conserved dual function in life and death.
- This dual functionality has significant pathophysiological implications, potentially explaining resistance to oncogenic mutations targeting apoptosis.
- Therapeutic interventions aimed at suppressing unwanted cell death must selectively target the lethal functions without disrupting the essential life-sustaining roles of these proteins.
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01:31The Intrinsic Apoptotic Pathway
01:24Caspases
01:30Apoptosis
01:17The Extrinsic Apoptotic Pathway
01:22Cellular Injury V: Apoptosis and Autophagy
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...