Autophagosome biogenesis by the core Atg machinery in Drosophila melanogaster

Macroautophagy begins with formation of a cup-shaped phagophore that expands and closes to form the double-membrane autophagosome. The core Atg proteins act in conserved functional units. The Atg1 kinase complex (Atg1, Atg13, Atg17/FIP200 and Atg101) initiates phagophore formation in response to nutrient starvation and TOR inhibition. The class III phosphatidylinositol 3-kinase complex (Vps34/Pi3K59F, Vps15, Atg6/Beclin 1 and Atg14) produces phosphatidylinositol 3-phosphate at the phagophore. Atg9 vesicles supply membrane and Atg9 has phospholipid scramblase activity, while Atg2, recruited with the PI3P-binding Atg18 proteins, transfers lipids to the expanding phagophore. Two ubiquitin-like conjugation systems act downstream: Atg7 and Atg10 conjugate Atg12 to Atg5, and the Atg12-Atg5-Atg16 complex promotes lipidation of Atg8 proteins with phosphatidylethanolamine by Atg7 and Atg3 after processing of Atg8 by the Atg4 proteases. In Drosophila, the fat body of starved larvae is the classic setting for studying this pathway.

MODULE:dmel_autophagosome_biogenesisDRAFTCONCRETEBiological Processmodules/dmel_autophagosome_biogenesis.yaml
autophagosome assemblyGO:0000045
FB:FBgg0000076
FlyBase gene group ATG: Autophagy-related genes
FlyBase release FB2026_03 groups 20 D. melanogaster genes as autophagy-related genes (ATG); this module models that group.
FB:FBgg0000216
FlyBase gene group ATG-CPX: Autophagy-related complexes
FlyBase release FB2026_03 groups 11 D. melanogaster genes as autophagy-related complexes (ATG-CPX); this module models that group.
GO:0000045
autophagosome assembly
GO term grounding the module as autophagosome assembly.

Boundary. The module contains the FlyBase core Atg genes and the Atg complexes. Pi3K59F and Vps15 enter through the FlyBase autophagy-specific PI3 kinase complex group; they also act in endosomal PI3K complexes. Atg7 is placed in both conjugation systems because it is the E1 enzyme for both Atg12 and Atg8. Autophagosome-lysosome fusion (HOPS, SNAREs), cargo receptors and upstream TOR signalling are outside the module. The connections give the conventional order of action; parts also act partly in parallel. FlyBase groups realized by this module: ATG (FBgg0000076), ATG-CPX (FBgg0000216). Subgroups folded into it: ATG-PK, ATG-C, ATG-PI3K. Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_autophagosome_biogenesis.yaml. None of the member genes has a gene review in this repository yet.

8Nodes
7Parts
0Variant Sets
0Variants
16Annotons
5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_autophagosome_biogenesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • atg1_kinase_complex → autophagy_pi3k_complex [NOT_CHECKED]
  • autophagy_pi3k_complex → atg2_atg18_lipid_transfer [NOT_CHECKED]
  • atg9_vesicles → atg2_atg18_lipid_transfer [NOT_CHECKED]

Function consistency and core coverage

0 gene-function check(s) reflected in core functions · 0 conflict(s) · 12 evidence or coverage gap(s) (12 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
atg1_kinase_complex_complex/atg1 Atg1
UniProtKB:Q9VU14
Complex Unit 		protein serine/threonine kinase activity
GO:0004674 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
autophagy_pi3k_complex_complex/pi3k59f Pi3K59F
UniProtKB:Q9W1M7
Complex Unit 		1-phosphatidylinositol-3-kinase activity
GO:0016303 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg9_vesicles_atg9 Atg9
UniProtKB:A0A0B4KF86
Gene 		phospholipid scramblase activity
GO:0017128 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg2_atg18_lipid_transfer_atg2 Atg2
UniProtKB:Q9VZX7
Gene 		lipid transfer activity
GO:0120013 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg2_atg18_lipid_transfer_atg18a Atg18a
UniProtKB:M9PER1
Gene 		phosphatidylinositol-3-phosphate binding
GO:0032266 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg2_atg18_lipid_transfer_atg18b Atg18b
UniProtKB:Q9VIE1
Gene 		phosphatidylinositol-3-phosphate binding
GO:0032266 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg12_conjugation_atg7 Atg7
UniProtKB:A1ZBA9
Gene 		Atg12 activating enzyme activity
GO:0019778 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg12_conjugation_atg10 Atg10
UniProtKB:A8DY59
Gene 		Atg12 transferase activity
GO:0019777 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg8_lipidation_atg4a Atg4a
UniProtKB:Q9VPW2
Gene 		cysteine-type endopeptidase activity
GO:0004197 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg8_lipidation_atg4b Atg4b
UniProtKB:Q9VF80
Gene 		cysteine-type endopeptidase activity
GO:0004197 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg8_lipidation_atg7 Atg7
UniProtKB:A1ZBA9
Gene 		Atg8 activating enzyme activity
GO:0019779 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
atg8_lipidation_atg3 Atg3
UniProtKB:Q9VVS6
Gene 		Atg8-family ligase activity
GO:0019776 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.

Gene-review completeness (0/22 grounded genes reviewed)

0 complete review(s) · 0 with deep research · 22 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
Atg9 A0A0B4KF86 ✗ — —
Atg7 A1ZBA9 ✗ — —
Atg10 A8DY59 ✗ — —
Atg16 B7Z0R7 ✗ — —
Atg18a M9PER1 ✗ — —
Atg17 Q7KTS2 ✗ — —
Atg14 Q9VAP6 ✗ — —
Atg6 Q9VCE1 ✗ — —
Atg8b Q9VEG5 ✗ — —
Atg4b Q9VF80 ✗ — —
Vps15 Q9VHH2 ✗ — —
Atg13 Q9VHR6 ✗ — —
Atg18b Q9VIE1 ✗ — —
Atg4a Q9VPW2 ✗ — —
Atg12 Q9VTU1 ✗ — —
Atg1 Q9VU14 ✗ — —
Atg3 Q9VVS6 ✗ — —
Atg101 Q9VWQ1 ✗ — —
Atg2 Q9VZX7 ✗ — —
Pi3K59F Q9W1M7 ✗ — —
Atg8a Q9W2S2 ✗ — —
Atg5 Q9W3R7 ✗ — —

Details

Context
Drosophila melanogasterNCBITaxon:7227
phagophore assembly siteGO:0000407
Autophagosome biogenesisBiological Processdmel_autophagosome_biogenesis

Core Atg kinase, lipid kinase, lipid transfer and ubiquitin-like conjugation units that build the autophagosome.

autophagosome assemblyGO:0000045
Context
Drosophila melanogasterNCBITaxon:7227
phagophore assembly siteGO:0000407

Connections

The Atg1 complex initiates phagophore formation and recruits the PI3K complex.
PI3P made by the PI3K complex recruits Atg18 with Atg2.
Atg9 vesicles seed the phagophore that Atg2 expands by lipid transfer.
Atg7 and Atg10 form the Atg12-Atg5 conjugate that assembles with Atg16.
atg12_atg5_atg16_complex -> atg8_lipidation Positively Regulates
The Atg12-Atg5-Atg16 complex promotes Atg3-mediated Atg8 lipidation.
Part 1: initiation kinase complex
Atg1 kinase complexBiological Processatg1_kinase_complex

Annotons

Atg1 kinase complex
atg1_kinase_complex_complex
Participant: Protein Complex: Atg1 kinase complex
Protein Complex:
Atg1 kinase complexGO:1990316
Active units:
Atg1
Participant: Gene Product: Atg1
Gene Product:
Atg1UniProtKB:Q9VU14
Function:
protein serine/threonine kinase activityGO:0004674
Atg101
Participant: Gene Product: Atg101
Gene Product:
Atg101UniProtKB:Q9VWQ1
Atg13
Participant: Gene Product: Atg13
Gene Product:
Atg13UniProtKB:Q9VHR6
Atg17
Participant: Gene Product: Atg17
Gene Product:
Atg17UniProtKB:Q7KTS2
Part 2: PI3P production at the phagophore
Autophagy-specific class III PI3K complexBiological Processautophagy_pi3k_complex

Annotons

Autophagy-specific class III PI3K complex
autophagy_pi3k_complex_complex
Participant: Protein Complex: Autophagy-specific class III PI3K complex
Protein Complex:
Autophagy-specific class III PI3K complexGO:0035032
Active units:
Atg14
Participant: Gene Product: Atg14
Gene Product:
Atg14UniProtKB:Q9VAP6
Atg6
Participant: Gene Product: Atg6
Gene Product:
Atg6UniProtKB:Q9VCE1
Pi3K59F
Participant: Gene Product: Pi3K59F
Gene Product:
Pi3K59FUniProtKB:Q9W1M7
Function:
1-phosphatidylinositol-3-kinase activityGO:0016303
Vps15
Participant: Gene Product: Vps15
Gene Product:
Vps15UniProtKB:Q9VHH2
Part 3: membrane source and lipid scrambling
Atg9Biological Processatg9_vesicles

Annotons

Atg9 Atg9
atg9_vesicles_atg9
Participant: Gene Product: Atg9
Gene Product:
Atg9UniProtKB:A0A0B4KF86

Function

phospholipid scramblase activityGO:0017128
Part 4: lipid transfer to the phagophore
Atg2-Atg18 lipid transfer unitBiological Processatg2_atg18_lipid_transfer

Annotons

Atg2 Atg2-Atg18 lipid transfer unit
atg2_atg18_lipid_transfer_atg2
Participant: Gene Product: Atg2
Gene Product:
Atg2UniProtKB:Q9VZX7

Function

lipid transfer activityGO:0120013
Atg18a Atg2-Atg18 lipid transfer unit
atg2_atg18_lipid_transfer_atg18a
Participant: Gene Product: Atg18a
Gene Product:
Atg18aUniProtKB:M9PER1

Function

phosphatidylinositol-3-phosphate bindingGO:0032266
Atg18b Atg2-Atg18 lipid transfer unit
atg2_atg18_lipid_transfer_atg18b
Participant: Gene Product: Atg18b
Gene Product:
Atg18bUniProtKB:Q9VIE1

Function

phosphatidylinositol-3-phosphate bindingGO:0032266
Part 5: Atg12-Atg5 conjugation
Atg12 conjugation systemBiological Processatg12_conjugation

Annotons

Atg7 Atg12 conjugation system
atg12_conjugation_atg7
Participant: Gene Product: Atg7
Gene Product:
Atg7UniProtKB:A1ZBA9

Function

Atg12 activating enzyme activityGO:0019778
Atg10 Atg12 conjugation system
atg12_conjugation_atg10
Participant: Gene Product: Atg10
Gene Product:
Atg10UniProtKB:A8DY59

Function

Atg12 transferase activityGO:0019777
Atg12 Atg12 conjugation system
atg12_conjugation_atg12
Participant: Gene Product: Atg12
Gene Product:
Atg12UniProtKB:Q9VTU1
Part 6: E3-like complex for Atg8 lipidation
Atg12-Atg5-Atg16 complexBiological Processatg12_atg5_atg16_complex

Annotons

Atg12-Atg5-Atg16 complex
atg12_atg5_atg16_complex_complex
Participant: Protein Complex: Atg12-Atg5-Atg16 complex
Protein Complex:
Atg12-Atg5-Atg16 complexGO:0034274
Active units:
Atg12
Participant: Gene Product: Atg12
Gene Product:
Atg12UniProtKB:Q9VTU1
Atg16
Participant: Gene Product: Atg16
Gene Product:
Atg16UniProtKB:B7Z0R7
Atg5
Participant: Gene Product: Atg5
Gene Product:
Atg5UniProtKB:Q9W3R7
Part 7: Atg8 processing and conjugation to phosphatidylethanolamine
Atg8 processing and lipidation systemBiological Processatg8_lipidation

Annotons

Atg4a Atg8 processing and lipidation system
atg8_lipidation_atg4a
Participant: Gene Product: Atg4a
Gene Product:
Atg4aUniProtKB:Q9VPW2

Function

cysteine-type endopeptidase activityGO:0004197
Atg4b Atg8 processing and lipidation system
atg8_lipidation_atg4b
Participant: Gene Product: Atg4b
Gene Product:
Atg4bUniProtKB:Q9VF80

Function

cysteine-type endopeptidase activityGO:0004197
Atg7 Atg8 processing and lipidation system
atg8_lipidation_atg7
Participant: Gene Product: Atg7
Gene Product:
Atg7UniProtKB:A1ZBA9

Function

Atg8 activating enzyme activityGO:0019779
Atg3 Atg8 processing and lipidation system
atg8_lipidation_atg3
Participant: Gene Product: Atg3
Gene Product:
Atg3UniProtKB:Q9VVS6

Function

Atg8-family ligase activityGO:0019776
Atg8a Atg8 processing and lipidation system
atg8_lipidation_atg8a
Participant: Gene Product: Atg8a
Gene Product:
Atg8aUniProtKB:Q9W2S2
Atg8b Atg8 processing and lipidation system
atg8_lipidation_atg8b
Participant: Gene Product: Atg8b
Gene Product:
Atg8bUniProtKB:Q9VEG5