ATG2A is a large lipid-transfer protein that bridges donor membranes and the phagophore during autophagosome biogenesis. It binds and transfers glycerophospholipids, cooperates with WIPI/Atg18-family phosphoinositide effectors and ATG9A, and supplies membrane for phagophore expansion. Characterized donor contacts include the endoplasmic reticulum and ANKFY1-dependent endosome-phagophore contacts. ATG2A also associates with lipid droplets and ER-mitochondria contact sites.
Definition: The open edge of a phagophore at which its two apposed membrane sheets are joined, characterised by a dilated intermembrane lumen and by a distinct set of resident proteins, and which is sealed by membrane abscission at phagophore closure.
Justification: Cryo-electron tomography shows the intermembrane lumen is dilated specifically at the rim, and the rim is where the phagophore contacts the ER. The compartment is defined by residents, not only by shape - ATG2 with the Atg18/WIPI propellers, and Atg24/Snx4 with Atg20 or Snx41, are rim-localised. GO already models the analogous structure for an expanding cup-shaped membrane as GO:0097203 phagocytic cup lip. An alternative label, "phagophore edge", follows GO's dominant naming for this pattern. See GO issue #29437 (recommendation R7).
Parent term: phagophore
Definition: A zone of apposition between the endoplasmic reticulum membrane and the phagophore, bridged by ATG2-family lipid transfer proteins together with Atg18/WIPI-family PI3P effectors and the ATG9 scramblase, across which glycerophospholipids are delivered to support phagophore expansion.
Justification: GO models many other contact sites explicitly (GO:0044233, GO:0140268, GO:0120095 vacuole-isolation membrane contact site) but has nothing for the phagophore-ER apposition, which is the best-characterised of the phagophore's contacts. See GO issue #29437 (recommendation R7) and modules/phagophore_organelle_contact_site.yaml.
Parent term: organelle membrane contact site
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000407 phagophore assembly site | IBA GO_REF:0000033 | ACCEPT | Summary: ATG2A acts at the phagophore assembly site during autophagosome biogenesis. Reason: Accept as a core location/context. Human ATG2A localizes to ER-phagophore/autophagophore contact sites and functions in lipid transfer during phagophore expansion; the IBA assignment is consistent with direct human evidence and the conserved ATG2/Atg18 autophagy module. Supporting Evidence: PMID:30952800 localization of human ATG2A to contact sites between the ER and the autophagophore file:human/ATG2A/ATG2A-uniprot.txt Localizes to endoplasmic reticulum-autophagosome contact sites. |
| GO:0000422 autophagy of mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the selective-autophagy context for conserved membrane-supply machinery. Reason: Participation in autophagy of mitochondrion does not require ATG2A to recognize the cargo or have a pathway-exclusive function. ATG2A performs lipid-transfer and membrane-tethering work during phagophore expansion, rather than merely being a consumed substrate. The PAINT assertion at PTN000324023 is consistent with this conserved contribution; the previous demand for ATG2A-specific cargo selection was not a valid reason to replace it with a generic process. Retain as a context of the core machinery without claiming a direct human cargo-recognition assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000324023 · PTN000324023 SUPPORTS TRANSFER The cached IBD places selective-autophagy participation on the ATG2 ancestor. General lipid-supply work can be used by multiple cargo pathways; absence of exclusive cargo recognition does not demonstrate loss. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro |
| GO:0061908 phagophore | IBA GO_REF:0000033 | ACCEPT | Summary: ATG2A is active at the expanding phagophore. Reason: Accept as a core cellular context. ATG2A is placed at the phagophore/ER interface and promotes phagophore expansion by lipid transfer and tethering. Supporting Evidence: PMID:31271352 we place the ATG2-WIPI complex between the ER and the phagophore edge file:human/ATG2A/ATG2A-uniprot.txt Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) |
| GO:0000425 pexophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the selective-autophagy context for conserved membrane-supply machinery. Reason: Participation in pexophagy does not require ATG2A to recognize the cargo or have a pathway-exclusive function. ATG2A performs lipid-transfer and membrane-tethering work during phagophore expansion, rather than merely being a consumed substrate. The PAINT assertion at PTN000324023 is consistent with this conserved contribution; the previous demand for ATG2A-specific cargo selection was not a valid reason to replace it with a generic process. Retain as a context of the core machinery without claiming a direct human cargo-recognition assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000324023 · PTN000324023 SUPPORTS TRANSFER The cached IBD places selective-autophagy participation on the ATG2 ancestor. General lipid-supply work can be used by multiple cargo pathways; absence of exclusive cargo recognition does not demonstrate loss. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATG2A has a core membrane-adaptor/tethering role at ER-phagophore contact sites. Reason: Accept as a core molecular function. ATG2A couples WIPI/Atg18-family PI3P effectors, ATG9A-containing membranes, and ER/phagophore membranes in a lipid-transfer assembly. This term captures the adaptor/tether aspect of the function alongside the more direct lipid transfer activity term. Supporting Evidence: PMID:31271352 ATG2 stably tethers two membranes and transfers lipids between them PMID:39174844 ATG2A tethers lipid vesicles at different orientations |
| GO:0061723 glycophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the selective-autophagy context for conserved membrane-supply machinery. Reason: Participation in glycophagy does not require ATG2A to recognize the cargo or have a pathway-exclusive function. ATG2A performs lipid-transfer and membrane-tethering work during phagophore expansion, rather than merely being a consumed substrate. The PAINT assertion at PTN000324023 is consistent with this conserved contribution; the previous demand for ATG2A-specific cargo selection was not a valid reason to replace it with a generic process. Retain as a context of the core machinery without claiming a direct human cargo-recognition assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000324023 · PTN000324023 SUPPORTS TRANSFER The cached IBD places selective-autophagy participation on the ATG2 ancestor. General lipid-supply work can be used by multiple cargo pathways; absence of exclusive cargo recognition does not demonstrate loss. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: Direct ancestral PI3P-binding evidence supports retaining the molecular-function inference. Reason: The PTN000324023 IBD is seeded by yeast ATG2. QuickGO traces its IDA to PMID:27498190, which directly shows phosphoinositide binding by an isolated Atg2 APT1-containing region, especially PI3P. Human ATG2A membrane recruitment is enhanced by WIPI proteins (PMID:31271352), but an adaptor-mediated recruitment route does not demonstrate loss of ATG2 lipid binding. Retain the family inference with the distinction between direct donor binding and human membrane-recruitment assays explicit. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000324023 · PTN000324023 SUPPORTS TRANSFER Yeast ATG2 has direct IDA evidence from its isolated lipid-binding region (PMID:27498190); WIPI-dependent human recruitment is not a negative binding experiment. Supporting Evidence: PMID:27498190 this domain is able to bind phosphatidylinositol phosphates, especially PI3P PMID:31271352 WIPI4 and ATG2A cooperatively associate with PI3P-containing membranes |
| GO:0034727 piecemeal microautophagy of the nucleus | IBA GO_REF:0000033 | UNDECIDED | Summary: Human participation in this nuclear microautophagy route remains unresolved. Reason: GO:0034727 denotes degradation of a cell nucleus by microautophagy. The yeast-seeded PTN000324023 assertion is genuine; its single donor is not a weakness. However, conservation of the particular microautophagic route and the work performed by human ATG2A need evaluation separately from general macroautophagosome membrane supply. The prior generic replacement obscured this unresolved pathway question. The completed OpenScientist report recommends removal because the characterized yeast route uses Nvj1-Vac8 nuclear-vacuolar junctions and its PANTHER search found no human orthologs of those components. This is relevant mechanistic divergence, not merely absence of a target assay. However, the report itself calls for independent orthology and structural confirmation, and its claim that mammals have no vacuole does not resolve whether lysosomal functional equivalents or alternative junction machinery fall within the process definition. Retain UNDECIDED pending a second opinion on that precise route-equivalence question; the existing report has been considered and should not be rerun. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000324023 · PTN000324023 UNRESOLVED The cached yeast-seeded IBD is confirmed; human nuclear microautophagy route conservation remains unresolved, independently of donor count. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro |
| GO:0061709 reticulophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the selective-autophagy context for conserved membrane-supply machinery. Reason: Participation in reticulophagy does not require ATG2A to recognize the cargo or have a pathway-exclusive function. ATG2A performs lipid-transfer and membrane-tethering work during phagophore expansion, rather than merely being a consumed substrate. The PAINT assertion at PTN000324023 is consistent with this conserved contribution; the previous demand for ATG2A-specific cargo selection was not a valid reason to replace it with a generic process. Retain as a context of the core machinery without claiming a direct human cargo-recognition assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000324023 · PTN000324023 SUPPORTS TRANSFER The cached IBD places selective-autophagy participation on the ATG2 ancestor. General lipid-supply work can be used by multiple cargo pathways; absence of exclusive cargo recognition does not demonstrate loss. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ER membrane localization is supported and central to ATG2A function. Reason: Accept. UniProt subcellular-location mapping agrees with direct human evidence placing ATG2A at ER-autophagosome/phagophore contact sites, where it mediates lipid transfer from ER-associated donor membranes. Supporting Evidence: PMID:30952800 operating at the ER-autophagosome interface file:human/ATG2A/ATG2A-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005811 lipid droplet | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Lipid-droplet association is supported but secondary to the core autophagosome-biogenesis role. Reason: Lipid-droplet association and effects on lipid-droplet morphology are documented ancillary contexts. Retain without treating the principal ER/endosome-to-phagophore lipid-supply role as exclusive localization. Supporting Evidence: file:human/ATG2A/ATG2A-uniprot.txt Also regulates lipid droplets morphology and distribution within the cell |
| GO:0006914 autophagy | IEA GO_REF:0000002 | MODIFY | Summary: Autophagy is correct but too broad for the reviewed ATG2A process. Reason: ATG2A is not merely associated with generic autophagy; direct experiments support a more specific role in autophagosome assembly through phagophore expansion and lipid transfer. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:30952800 lipid transfer across contact sites is a principal contributor to autophagosome formation PMID:31271352 ATG2-mediated transfer of lipids from the ER to the phagophore enables phagophore expansion |
| GO:0034045 phagophore assembly site membrane | IEA GO_REF:0000044 | MODIFY | Summary: Replace the now-obsolete PAS-membrane term with phagophore membrane. Reason: Live QuickGO checked 2026-09-20 marks GO:0034045 obsolete and supplies GO:7770114 phagophore membrane as the relevant replacement. PMID:31271352 places ATG2-WIPI between ER and phagophore edge, supporting membrane-associated residence there. This supersedes the older statement that no replacement exists; preserve the original GOA identifier as source metadata. Proposed replacements: phagophore membrane Supporting Evidence: PMID:31271352 we place the ATG2-WIPI complex between the ER and the phagophore edge |
| GO:0120009 intermembrane lipid transfer | IEA GO_REF:0000108 | ACCEPT | Summary: ATG2A mediates intermembrane lipid transfer during phagophore expansion. Reason: Accept as a core biological process. The logical inference from lipid transfer activity is directly consistent with in vitro lipid-transfer assays, structural work, and cellular rescue data. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro PMID:39174844 mediating lipid transfer and re-equilibration between membranes for autophagosome formation |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | REMOVE | Summary: The interaction evidence is useful, but generic protein binding is uninformative. Reason: Specific lipid transfer, membrane recruitment and ATG2-WIPI complex assembly capture ATG2A function. Removal of generic protein binding follows project policy and does not assert that the underlying interaction is false. Supporting Evidence: PMID:20562859 a network of 751 interactions among 409 candidate interacting proteins PMID:31271352 ATG2 stably tethers two membranes and transfers lipids between them |
| GO:0005515 protein binding | IPI PMID:31412244 TOM40 Targets Atg2 to Mitochondria-Associated ER Membranes f... | REMOVE | Summary: The interaction evidence is useful, but generic protein binding is uninformative. Reason: Specific lipid transfer, membrane recruitment and ATG2-WIPI complex assembly capture ATG2A function. Removal of generic protein binding follows project policy and does not assert that the underlying interaction is false. Supporting Evidence: PMID:31412244 Atg2A directly interacts with Atg9A at the MAM to promote phagophore growth PMID:31412244 TOM70-TOM40 complex recruits Atg2A to the MAM |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The interaction evidence is useful, but generic protein binding is uninformative. Reason: Specific lipid transfer, membrane recruitment and ATG2-WIPI complex assembly capture ATG2A function. Removal of generic protein binding follows project policy and does not assert that the underlying interaction is false. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32483132 Multi-site-mediated entwining of the linear WIR-motif around... | REMOVE | Summary: The interaction evidence is useful, but generic protein binding is uninformative. Reason: Specific lipid transfer, membrane recruitment and ATG2-WIPI complex assembly capture ATG2A function. Removal of generic protein binding follows project policy and does not assert that the underlying interaction is false. Supporting Evidence: PMID:32483132 WIPI4 forms a complex with ATG2A/B PMID:32483132 disrupt the interactions between WIPI3/4 and ATG2A and impair the ATG2A-mediated autophagic process |
| GO:0010508 positive regulation of autophagy | IMP PMID:32483132 Multi-site-mediated entwining of the linear WIR-motif around... | MODIFY | Summary: ATG2A-WIPI disruption impairs autophagy, but ATG2A is core assembly machinery rather than only a regulator. Reason: The evidence shows that disrupting ATG2A-WIPI interactions impairs the ATG2A-mediated autophagic process. For ATG2A itself, the more direct process term is autophagosome assembly. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:32483132 impair the ATG2A-mediated autophagic process PMID:31271352 Direct tethering of the ER and the phagophore edge by the ATG2-WIPI complex |
| GO:0120013 lipid transfer activity | IMP PMID:39174844 Structural basis for lipid transfer by the ATG2A-ATG9A compl... | ACCEPT | Summary: Structural data support ATG2A lipid transfer activity with ATG9A/WIPI4 complexes. Reason: Accept as core molecular function. Structural and mechanistic evidence supports ATG2A as a lipid-transfer protein whose cavity and ATG9A/WIPI4-associated assemblies mediate lipid transfer during autophagosome formation. Supporting Evidence: PMID:39174844 Structural basis for lipid transfer by the ATG2A-ATG9A complex PMID:39174844 human ATG2A in complex with WD-repeat protein interacting with phosphoinositides 4 |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:30952800 ATG2 transports lipids to promote autophagosome biogenesis. | ACCEPT | Summary: Direct evidence places ATG2A at the ER/autophagosome interface. Reason: Accept. This experimentally supported location is central to ATG2A's lipid-transfer function during phagophore expansion. Supporting Evidence: PMID:30952800 operating at the ER-autophagosome interface file:human/ATG2A/ATG2A-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005811 lipid droplet | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Lipid-droplet localization is supported by homology/UniProt but is non-core for this review. Reason: Lipid-droplet association and effects on lipid-droplet morphology are documented ancillary contexts. Retain without treating the principal ER/endosome-to-phagophore lipid-supply role as exclusive localization. Supporting Evidence: file:human/ATG2A/ATG2A-uniprot.txt Lipid droplet |
| GO:0034045 phagophore assembly site membrane | EXP PMID:30952800 ATG2 transports lipids to promote autophagosome biogenesis. | MODIFY | Summary: Replace the now-obsolete PAS-membrane term with phagophore membrane. Reason: Live QuickGO checked 2026-09-20 marks GO:0034045 obsolete and supplies GO:7770114 phagophore membrane as the relevant replacement. PMID:31271352 places ATG2-WIPI between ER and phagophore edge, supporting membrane-associated residence there. This supersedes the older statement that no replacement exists; preserve the original GOA identifier as source metadata. Proposed replacements: phagophore membrane Supporting Evidence: PMID:31271352 we place the ATG2-WIPI complex between the ER and the phagophore edge |
| GO:0044232 organelle membrane contact site | IDA PMID:30952800 ATG2 transports lipids to promote autophagosome biogenesis. | ACCEPT | Summary: ATG2A is active at organelle membrane contact sites during autophagosome formation. Reason: Accept. ATG2A is a contact-site lipid-transfer protein, with direct evidence for ER-autophagophore localization and functional lipid transfer across membranes. Supporting Evidence: PMID:30952800 protein-mediated lipid transfer across contact sites is a principal contributor PMID:31271352 ATG2 stably tethers two membranes and transfers lipids between them |
| GO:0120013 lipid transfer activity | IDA PMID:30952800 ATG2 transports lipids to promote autophagosome biogenesis. | ACCEPT | Summary: Direct biochemical evidence supports ATG2A lipid transfer activity. Reason: Accept as core molecular function. Purified human ATG2A binds multiple glycerophospholipids and transfers lipids between membranes in vitro, and lipid-transfer-competent ATG2A fragments rescue autophagosome biogenesis. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro PMID:30952800 fully sufficient to rescue blocked autophagosome biogenesis in ATG2A/ATG2B KO cells |
| GO:0120013 lipid transfer activity | IDA PMID:31271352 The autophagic membrane tether ATG2A transfers lipids betwee... | ACCEPT | Summary: ATG2A lipid transfer activity is directly demonstrated and WIPI-facilitated. Reason: Accept as core molecular function. This study directly demonstrates human ATG2A lipid transfer, membrane tethering, and WIPI-enhanced association with PI3P-containing membranes. Supporting Evidence: PMID:31271352 human ATG2A is a lipid transfer protein PMID:31271352 WIPI proteins can facilitate ATG2A-mediated lipid transfer |
| GO:2000786 positive regulation of autophagosome assembly | IDA PMID:30952800 ATG2 transports lipids to promote autophagosome biogenesis. | MODIFY | Summary: ATG2A directly participates in autophagosome assembly rather than only regulating it. Reason: ATG2A lipid transfer supplies membrane for phagophore expansion, making autophagosome assembly the more direct process term. The regulation term is directionally true but less precise for a core autophagy machinery component. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:30952800 protein-mediated lipid transfer across contact sites is a principal contributor to autophagosome formation PMID:30952800 rescue blocked autophagosome biogenesis in ATG2A/ATG2B KO cells |
| GO:2000786 positive regulation of autophagosome assembly | IDA PMID:31271352 The autophagic membrane tether ATG2A transfers lipids betwee... | MODIFY | Summary: WIPI-facilitated ATG2A lipid transfer supports autophagosome assembly. Reason: The direct functional role is phagophore expansion/autophagosome assembly via lipid transfer. Use autophagosome assembly rather than a regulation term for this core machinery activity. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:31271352 transfer of ER lipids to the phagophore, driving phagophore expansion PMID:31271352 WIPI proteins can facilitate ATG2A-mediated lipid transfer |
| GO:0000045 autophagosome assembly | IMP PMID:28561066 WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-... | ACCEPT | Summary: ATG2A is a core autophagosome-assembly factor. Reason: Accept as core process. WIPI4-ATG2 translocates to nascent autophagosomes and later studies show ATG2A lipid transfer and tethering drive phagophore expansion. Supporting Evidence: PMID:28561066 WIPI4-ATG2 is released from a WIPI4-ATG2/AMPK-ULK1 complex and translocates to nascent autophagosomes PMID:30952800 protein-mediated lipid transfer across contact sites is a principal contributor to autophagosome formation |
| GO:0005515 protein binding | IPI PMID:28561066 WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-... | REMOVE | Summary: The interaction evidence is useful, but generic protein binding is uninformative. Reason: Specific lipid transfer, membrane recruitment and ATG2-WIPI complex assembly capture ATG2A function. Removal of generic protein binding follows project policy and does not assert that the underlying interaction is false. Supporting Evidence: PMID:28561066 WIPI4-ATG2 is released from a WIPI4-ATG2/AMPK-ULK1 complex PMID:31271352 we place the ATG2-WIPI complex between the ER and the phagophore edge |
| GO:0062079 ATG2-ATG18 complex | IDA PMID:31271352 The autophagic membrane tether ATG2A transfers lipids betwee... | NEW | Summary: The PN-projected ATG2-ATG18 complex term is a conservative, supported component annotation. Reason: Direct human ATG2A-WIPI structural and biochemical studies support membership of the ATG2-Atg18-family complex. Mammalian WIPI proteins are Atg18-family effectors, and PMID:39174844 directly resolves ATG2A-WIPI4 and ATG2A-WIPI4-ATG9A assemblies. This is a complex-membership assertion, not an inference of every cargo-selective pathway. Supporting Evidence: PMID:31271352 we place the ATG2-WIPI complex between the ER and the phagophore edge PMID:32483132 WIPI4 forms a complex with ATG2A/B file:projects/PROTEOSTASIS/mappings/autophagy_lysosome_pathway.yaml The GO ATG2-ATG18 complex term is the closest component-level target. |
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Download this section (compressed HTML)Q: How is the direct PI3P-binding activity of the yeast Atg2 APT1 region conserved in human ATG2A, and how does it cooperate with WIPI- and ANKFY1-mediated recruitment?
Suggested experts: GO autophagy editors, autophagy lipid-transfer experts
Q: Does human ATG2A directly participate in nuclear microautophagy, and which selective macroautophagy contexts use its conserved lipid-supply activity? Cargo recognition is not required for participation by this membrane-supply machinery.
Suggested experts: GO autophagy editors, Proteostasis Consortium ALP curators
Q: Should GO:0062079 be updated to explicitly mention mammalian ATG2-WIPI complexes, since the current definition names the Saccharomyces cerevisiae ATG2-ATG18 composition?
Suggested experts: GO cellular-component editors, ComplexPortal curators
Q: What determines use of ER versus ANKFY1-dependent endosomal lipid donors by ATG2A during phagophore expansion?
Suggested experts: GO autophagy editors, autophagy membrane-contact-site experts
Q: Does human ATG2A (as opposed to ATG2B) have a direct, LIR/ATG8-dependent role in non-canonical autophagy (CASM) and lysosome repair upon lysosomal damage, distinct from its WIPI4-dependent canonical phagophore-expansion function?
Suggested experts: GO autophagy editors, lysosome biology experts
Experiment: Rescue ATG2A/ATG2B double-knockout human cells with ATG2A variants that selectively disrupt WIPI binding, TOM40/MAM targeting, or ATG9A association, then quantify mitophagy, pexophagy, ER-phagy, and glycophagy reporters alongside bulk autophagic flux.
Hypothesis: ATG2A is required for selective-autophagy reporter completion primarily through its general phagophore-expansion function, not through cargo-specific recognition.
Type: Selective-autophagy separation-of-function rescue
Experiment: Use starvation time courses with endogenous tagging or proximity labeling of ATG2A, WIPI1/2/3/4, and ATG9A, followed by quantitative proteomics and imaging at ER-phagophore contact sites.
Hypothesis: Human ATG2A participates in condition- and stage-specific ATG2-WIPI/Atg18 complexes whose component composition explains the PN-projected ATG2-ATG18 complex annotation.
Type: Endogenous ATG2-WIPI complex composition assay
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