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Updated: Jul 3, 2026

Detection and Isolation of Apoptotic Bodies to High Purity
Published on: August 12, 2018
Apoptosome assembly
1Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey, USA.
Abstract:
Apoptosome refers to the multimeric protein complex that mediates activation of an initiator caspase at the onset of apoptosis. This chapter describes the assembly of three related apoptosomes from mammals, fruit flies, and worms. The assembly of the mammalian apoptosome, which is responsible for the activation of caspase-9, involves Apaf-1 and requires cytochrome c and ATP/dATP binding. Assembly of the apoptosome in Drosophila melanogaster, which activates caspase-9 homologue Dronc, involves the Apaf-1 homologue known as Dark/Hac-1/Dapaf-1. In Caenorhabditis elegans, assembly of the CED-4 apoptosome requires EGL-1-mediated dissociation of CED-9 (a Bcl-2 homologue) from the CED-4-CED-9 complex and subsequent oligomerization of CED-4. Recent biochemical and structural investigation revealed insights into the assembly and function of the various apoptosomes.
Insights
The apoptosome, a protein complex crucial for apoptosis, assembles differently across species. Mammalian, fruit fly, and worm apoptosomes utilize distinct proteins and mechanisms for caspase activation during programmed cell death.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The apoptosome is a key protein complex that initiates apoptosis by activating initiator caspases.
- Understanding apoptosome assembly is critical for comprehending programmed cell death pathways.
Purpose of the Study:
- To describe the assembly mechanisms of three related apoptosomes from mammals, fruit flies (Drosophila melanogaster), and worms (Caenorhabditis elegans).
- To highlight the conserved and divergent aspects of apoptosome formation across different species.
Main Methods:
- Comparative analysis of biochemical and structural data.
- Review of existing literature on apoptosome assembly in model organisms.
Main Results:
- Mammalian apoptosome assembly involves Apaf-1, cytochrome c, and ATP/dATP binding for caspase-9 activation.
- Drosophila melanogaster apoptosome assembly utilizes the Apaf-1 homologue Dark/Hac-1/Dapaf-1 to activate Dronc.
- Caenorhabditis elegans apoptosome assembly involves CED-4 oligomerization, regulated by EGL-1 and CED-9.
Conclusions:
- Apoptosome assembly pathways exhibit species-specific variations while serving the conserved function of initiating apoptosis.
- Biochemical and structural insights continue to elucidate the intricate mechanisms of apoptosome formation and function.
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