Intrinsic apoptotic signaling pathway module

Cell-intrinsic stress signals regulate BCL2-family mitochondrial permeabilization, cytochrome c release, apoptosome assembly, and initiator caspase-9 activation.

MODULE:intrinsic_apoptotic_signalingDRAFTSignaling Pathwaymodules/intrinsic_apoptotic_signaling.yaml
intrinsic apoptotic signaling pathwayGO:0097193
file:modules/intrinsic_apoptotic_signaling-deep-research-falcon.md
Intrinsic apoptotic signaling pathway Falcon module review
Falcon/Edison module review generated 2026-06-28 is linked as supporting evidence for module boundaries, core mechanism, variation, constraints, and failure modes; open questions in that report require manual review before promotion to curated knowledge gaps.
GO:0097193
intrinsic apoptotic signaling pathway
The module is grounded in the GO biological process term for intrinsic apoptotic signaling pathway.
PANTHER:PTN000047947
PAINT node PTN000047947 for CASP9
Local PAINT IBD node in PTHR10454 with propagated terms C:GO:0005737, F:GO:0004197, P:GO:0006915; PAINT date 20260528.
PANTHER:PTN000238899
PAINT node PTN000238899 for CYCS
Local PAINT IBD node in PTHR11961 with propagated terms C:GO:0005758; PAINT date 20170228.
PANTHER:PTN008306143
PAINT node PTN008306143 for CASP9
Local PAINT IBD node in PTHR10454 with propagated terms C:GO:0005829; PAINT date 20260528.

Curated compact signaling-pathway module generated from verified UniProt exemplar accessions and local PAINT IBD rows. PTN anchors are included only when the exemplar accession appears in an IBD seed row in interpro/panther; roles without local PAINT seeds remain grounded by verified UniProt exemplar accessions. Falcon integration (2026-06-28): Falcon findings are linked as evidence and family-level support. Automatically extracted open-question headings were intentionally not retained as knowledge_gap entries because they were not manually curated. Machine-generated Falcon citations remain curation support and are not manually adjudicated here.

4Nodes
3Parts
0Variant Sets
0Variants
6Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • intrinsic_apoptotic_signaling-deep-research-falcon.md (falcon)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (3/5 grounded genes reviewed)

2 complete review(s) · 3 with deep research · 2 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
BCL2 P10415 ✓ 198/200 ✓
CASP9 P55211 ✓ ✓ ✓
CYCS P99999 ✓ ✓ ✓
APAF1 O14727 ✗ — —
BAX Q07812 ✗ — —

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
Intrinsic apoptotic signaling pathwaySignaling Pathwayintrinsic_apoptotic_signaling
intrinsic apoptotic signaling pathwayGO:0097193
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes cytochrome c apoptosome assembly.
Apoptosome assembly leads to initiator caspase activation.
Part 1: mitochondrial bcl2-family decision
BCL2-family mitochondrial decisionRegulatory Stepbcl2_family_mitochondrial_decision

BAX and BCL2 exemplify opposing BCL2-family control over mitochondrial outer membrane permeabilization.

Annotons

BAX pro-apoptotic effector
bax_bax_pro_apoptotic_effector
Participant: Gene Product: BAX
Gene Product:
BAXUniProtKB:Q07812

Curated exemplar for the bax pro-apoptotic effector role in intrinsic apoptotic signaling pathway.

BCL2 anti-apoptotic regulator
bcl2_bcl2_anti_apoptotic_regulator
Participant: Gene Product: BCL2
Gene Product:
BCL2UniProtKB:P10415

Curated exemplar for the bcl2 anti-apoptotic regulator role in intrinsic apoptotic signaling pathway.

Part 2: cytochrome c apoptosome assembly
Apoptosome assemblyRegulatory Stepapoptosome_assembly

Cytochrome c and APAF1 assemble the apoptosome platform.

Annotons

Cytochrome c
cycs_cytochrome_c
Participant: Family: Cytochrome c family/ortholog group
Family:
Cytochrome c family/ortholog groupPANTHER:PTHR11961
Representative Members: CYCSUniProtKB:P99999

Curated exemplar for the cytochrome c role in intrinsic apoptotic signaling pathway.

APAF1 apoptosome scaffold
apaf1_apaf1_apoptosome_scaffold
Participant: Gene Product: APAF1
Gene Product:
APAF1UniProtKB:O14727

Curated exemplar for the apaf1 apoptosome scaffold role in intrinsic apoptotic signaling pathway.

Part 3: initiator caspase activation
Caspase-9 activationRegulatory Stepcaspase_9_activation

The apoptosome recruits and activates caspase-9 to initiate intrinsic apoptosis.

Annotons

Caspase-9 initiator protease
casp9_caspase_9_initiator_protease
Participant: Family: Caspase-9 initiator protease family/ortholog group
Family:
Caspase-9 initiator protease family/ortholog groupPANTHER:PTHR10454
Representative Members: CASP9UniProtKB:P55211

Curated exemplar for the caspase-9 initiator protease role in intrinsic apoptotic signaling pathway.

Cytochrome c trigger
cycs_cytochrome_c_trigger
Participant: Family: Cytochrome c trigger family/ortholog group
Family:
Cytochrome c trigger family/ortholog groupPANTHER:PTHR11961
Representative Members: CYCSUniProtKB:P99999

Curated exemplar for the cytochrome c trigger role in intrinsic apoptotic signaling pathway.