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Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis
Published on: February 16, 2015
Mitochondrial pathway of apoptosis is ancestral in metazoans
Cheryl E Bender1, Patrick Fitzgerald, Stephen W G Tait
1Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Abstract:
The mitochondrial pathway of apoptosis is the major mechanism of physiological cell death in vertebrates. In this pathway, proapoptotic members of the Bcl-2 family cause mitochondrial outer membrane permeabilization (MOMP), allowing the release of cytochrome c, which interacts with Apaf-1 to trigger caspase activation and apoptosis. Despite conservation of Bcl-2, Apaf-1, and caspases in invertebrate phyla, the existence of the mitochondrial pathway in any invertebrate is, at best, controversial. Here we show that apoptosis in a lophotrochozoan, planaria (phylum Platyhelminthes), is associated with MOMP and that cytochrome c triggers caspase activation in cytosolic extracts from these animals. Further, planarian Bcl-2 family proteins can induce and/or regulate cell death in yeast and can replace Bcl-2 proteins in mammalian cells to regulate MOMP. These results suggest that the mitochondrial pathway of apoptosis in animals predates the emergence of the vertebrates but was lost in some lineages (e.g., nematodes). In further support of this hypothesis, we surveyed the ability of cytochrome c to trigger caspase activation in cytosolic extracts from a variety of organisms and found this effect in cytosolic extracts from invertebrate deuterostomes (phylum Echinodermata).
Insights
The study reveals that the mitochondrial apoptosis pathway, involving mitochondrial outer membrane permeabilization (MOMP), is present in planaria, an invertebrate. This finding suggests this cell death mechanism predates vertebrates but was lost in some lineages.
Area of Science:
- Cell Biology
- Evolutionary Biology
- Developmental Biology
Background:
- The mitochondrial pathway of apoptosis is crucial for cell death in vertebrates.
- This pathway involves mitochondrial outer membrane permeabilization (MOMP), cytochrome c release, and caspase activation.
- The presence of this pathway in invertebrates has been debated due to conserved but uncharacterized components.
Purpose of the Study:
- To investigate the existence and function of the mitochondrial apoptosis pathway in invertebrates.
- To determine if planaria utilize MOMP and cytochrome c for apoptosis.
- To explore the evolutionary origins of the mitochondrial apoptosis pathway.
Main Methods:
- Apoptosis assays in planaria.
- Analysis of cytochrome c's role in caspase activation using cytosolic extracts.
- Functional studies of planarian Bcl-2 proteins in yeast and mammalian cells.
- Survey of cytochrome c's effect on caspase activation across diverse organisms.
Main Results:
- Apoptosis in planaria is associated with MOMP and cytochrome c-triggered caspase activation.
- Planarian Bcl-2 proteins can regulate MOMP in heterologous systems.
- Cytochrome c triggers caspase activation in cytosolic extracts from invertebrate deuterostomes.
Conclusions:
- The mitochondrial apoptosis pathway likely predates the emergence of vertebrates.
- This pathway may have been lost in certain invertebrate lineages, such as nematodes.
- The findings provide evidence for the ancient evolutionary history of programmed cell death mechanisms.
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