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TitleLarge transient assemblies of Apaf1 constitute the apoptosome in cells.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 9429, Year 2025
Publish dateOct 24, 2025
AuthorsAlicia C Borgeaud / Iva Ganeva / Calvin Klein / Amandine Stooss / Daniela Ross-Kaschitza / Liyang Wu / Joel S Riley / Stephen W G Tait / Thomas Lemmin / Thomas Kaufmann / Wanda Kukulski /
PubMed AbstractUpon 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 ...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.
External linksNat Commun / PubMed:41136486 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-54278: Electron tomogram of resin-embedded, apoptosis-induced HeLa cell expressing Apaf1-GFP
Method: EM (tomography)

EMDB-54279: Cryo-electron tomogram of apoptosis-induced HeLa cell expressing Apaf1-GFP
Method: EM (tomography)

EMDB-54280: Cryo-electron tomogram of apoptosis-induced HeLa cell expressing Apaf1-SNAP
Method: EM (tomography)

EMDB-54281: Electron tomogram of resin-embedded, apoptosis-induced HeLa cell expressing Apaf1-GFP
Method: EM (tomography)

Source
  • Homo sapiens (human)

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