Large transient assemblies of Apaf1 constitute the apoptosome in cells

TL;DR

This study reveals that Apaf1 forms dynamic, cloud-like structures during apoptosis, which may represent the apoptosome in living cells.

Contribution

The study identifies transient Apaf1 assemblies as the apoptosome in cells, revealing their dynamic nature and role in apoptosis.

Findings

Apaf1 accumulates into multiple foci per cell during apoptosis.

Apaf1 foci resemble organelle-sized, cloud-like assemblies and depend on procaspase-9 for formation.

Disassembly of Apaf1 foci correlates with cell survival.

Abstract

Upon cell death signals, the apoptotic protease-activating factor Apaf1 and cytochrome c interact to form the apoptosome complex. The apoptosome is crucial for mitochondrial apoptosis, as it activates caspases that dismantle the cell. However, the in vivo assembly mechanism and appearance of the apoptosome remain unclear. We show that upon onset of apoptosis, Apaf1 molecules accumulate into multiple foci per cell. Disassembly of the foci correlates with cell survival. Structurally, Apaf1 foci resemble organelle-sized, cloud-like assemblies. They form through specific interactions with cytochrome c, contain caspase-9, and depend on procaspase-9 expression for their formation. We propose that Apaf1 foci correspond to the apoptosome in cells. Transientness and ultrastructure of Apaf1 foci suggest that the dynamic spatiotemporal organisation of apoptosome components regulates progression of apoptosis.

The apoptosome is known as a protein complex that initiates cell death. Here Borgeaud et al. reveal that in living cells, the apoptosome protein components assemble into dynamic meshwork-like structures that dissociate in cells surviving apoptosis.

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