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Published on: March 5, 2018
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Large transient assemblies of Apaf1 constitute the apoptosome in cells
Alicia C Borgeaud1,2, Iva Ganeva1,2, Calvin Klein1,3
1Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Nature Communications
|October 24, 2025
Summary
Apaf1 foci form the apoptosome complex during apoptosis. Their dynamic assembly and disassembly regulate cell death progression, offering new insights into mitochondrial apoptosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The apoptosome complex, formed by Apaf1 and cytochrome c, is essential for initiating mitochondrial apoptosis by activating caspases.
- The in vivo assembly process and structural characteristics of the apoptosome remain poorly understood.
Purpose of the Study:
- To elucidate the in vivo assembly mechanism and visual characteristics of the apoptosome.
- To investigate the role of Apaf1 foci in the context of apoptosis.
Main Methods:
- Cellular imaging to observe Apaf1 localization and foci formation.
- Biochemical assays to analyze the composition and interactions within Apaf1 foci.
- Genetic manipulation to assess the dependence on procaspase-9.
Main Results:
- Apaf1 molecules accumulate into distinct foci within cells upon apoptotic signaling.
- These Apaf1 foci are organelle-sized, cloud-like structures that interact with cytochrome c and contain caspase-9.
- The formation of these foci is dependent on procaspase-9 expression, and their disassembly correlates with cell survival.
Conclusions:
- Apaf1 foci represent the in vivo form of the apoptosome.
- The transient nature and ultrastructure of Apaf1 foci suggest that dynamic spatiotemporal organization of apoptotic components regulates apoptosis progression.
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