identifier: traitmech:000646
label: aggrephagy
definition: An autophagy phenotype in which a microbial cell selectively degrades
  protein aggregates through macroautophagic delivery to lysosomal or vacuolar compartments.
definition_source: DOI:10.1080/15548627.2026.2724473
trait_category: PHYSIOLOGY
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- traitmech:000638
evidence:
- reference: DOI:10.1080/15548627.2026.2724473
  snippet: Our findings indicate that heat shock triggers the targeted degradation
    of ubiquitinated protein aggregates, mediated by the macroaggrephagy receptor
    Cue5.
  notes: PMID:42647820. Scientific abstract directly read in DOI-matched Europe PMC
    metadata, separately from Abbreviations. Supports selective macroautophagic aggregate
    degradation in Saccharomyces cerevisiae. In the same heat-stress context, Cct2
    and polyQ-HTT vacuolar turnover is reported to be independent of canonical autophagy;
    that turnover is not positive aggrephagy evidence. Publisher full text returned
    HTTP 403; Methods, actual figures and strain provenance were not inspected.
- reference: DOI:10.1038/s44319-024-00275-7
  snippet: Deficiency in this interaction significantly weakens the association of
    Cct2 with Atg8.
  notes: PMID:39322741, PMC11549370. Scientific abstract and XML Introduction, Results
    Sec3-Sec7, Discussion Sec9 and yeast Methods Sec11 and Sec14-Sec16 were read.
    The quoted interaction is Atg11-Cct2. Yeast GFP-47Q cleavage and perturbations
    support solid-aggregate turnover; Ape1-P22L maturation alone is not complete cargo
    destruction. Synopsis S142 differs from scientific-abstract/Results S412; retain
    the discrepancy. Mammalian counterparts and phosphorylation sites are not interchangeable
    with yeast. Actual figures, supplements, Table EV1 and independent strain provenance
    were not inspected.
- reference: DOI:10.1016/j.cell.2014.05.048
  snippet: We thus propose that CUET proteins play a critical and ancient role in
    autophagic clearance of cytotoxic protein aggregates.
  notes: PMID:25042851. Scientific abstract directly read in DOI-matched Europe PMC
    metadata. Yeast Cue5/Rsp5 perturbations and polyQ responses are separate from
    human Tollip experiments; do not transfer human rescue to yeast or equate toxicity
    alone with flux. Full text, actual figures and strain provenance were not inspected.
    Linked Comment-in articles are not counted as independent primary evidence.
- reference: DOI:10.1080/27694127.2023.2236407
  snippet: Interestingly, Cue5/Tollip, a known autophagy receptor for aggrephagy,
    is dispensable for this inclusion body autophagy.
  notes: 'PMID:37680383, PMC10482306. Scientific abstract directly read in DOI-matched
    Europe PMC metadata. Boundary evidence: the authors distinguish Htt103QP/A-beta42
    inclusion-body clearance in budding yeast as IBophagy. Do not relabel it an unqualified
    Cue5-dependent aggrephagy observation. Complete full text and actual figures were
    not inspected; XML returned HTTP 500 and publisher access returned HTTP 403.'
discussions:
- discussion_id: aggrephagy-scope-and-ibophagy
  prompt: Review cargo boundaries and qualified process alignment.
  kind: CURATION_TODO
  status: OPEN
  rationale: Autophagy traitmech:000638 is the broader phenotype. Protein aggregation,
    disaggregation, proteasomal proteolysis, puncta, toxicity reduction or vacuolar
    localization alone is not selective macroautophagic degradation. GO:0035973, directly
    resolved at https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO%3A0035973,
    is a nonobsolete biological process for selective protein-aggregate degradation
    by macroautophagy, not an exact organismal phenotype. Retain that route qualifier
    and omit exact xrefs and synonyms. The 2023 study explicitly separates IBophagy
    from aggrephagy; do not infer an exact synonym, disjointness or a separate TraitRecord
    solely from its receptor differences. Their potential broader/narrower relationship
    needs human review. Proteaphagy traitmech:000645 concerns proteasomes as cargo,
    not ordinary aggregate proteolysis.
  posed_by: codex
  posed_date: '2026-10-06'
- discussion_id: aggrephagy-context-exemplars-and-mechanisms
  prompt: Resolve conditional mechanisms and natural exemplars.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: Do not make Cue5, Cct2, Atg11, ubiquitination, heat shock or one aggregate
    reporter universal requirements. The 2026 autophagy-independent turnover result
    does not negate the 2024 nutrient-rich solid-aggrephagy assay. Keep experimental
    cargo, conditions and readouts distinct. Resolve the 2024 Synopsis/Results residue
    discrepancy and inspect actual panels before accession-level mechanism curation.
    Canonical examples remain unset pending independent natural-strain provenance;
    engineered cargo and reporter/deletion assays are not natural exemplars. A protein
    graph requires native taxon-paired accessions and functional evidence. Recombinant
    E. coli protein production is not an aggrephagy observation, and human disease
    outcomes are not microbial trait evidence.
  posed_by: codex
  posed_date: '2026-10-06'
curation_history:
- timestamp: '2026-10-06T16:23:31Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Added selective macroautophagic protein-aggregate degradation with four
    DOI-backed scientific-abstract snippets and explicit IBophagy, conditional receptor
    and source-access limits. Ignored-and-hidden novelty checks, fresh seed and pinned
    METPO review found no exact record. Reserved METPO:1059900 in v522 using unchanged
    corrected parent context from v521. Deferred unverified natural exemplars, exact
    mappings and protein graphs.
  llm_assisted: true