Year: 2025
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G2025316877, G3092947936, Algebraic and logical aspects of knowledge processing, Cryo-focused ion beam scanning electron microscope to prepare cells for visualising their molecular architecture by electron cryo-tomography, Lipid transfer at organelle contact sites, Regulation, Molecular Functions and Pathophysiological Relevance of BOK, NCCR TransCure - From transport physiology to identification of therapeutic targets, G7995011149
OpenAlex ID: W4415517639