aggrephagy

traitmech:000646 · CLASS · PROPOSED

An autophagy phenotype in which a microbial cell selectively degrades protein aggregates through macroautophagic delivery to lysosomal or vacuolar compartments.

Trait evidence (4)

DOI:10.1080/15548627.2026.2724473
Our findings indicate that heat shock triggers the targeted degradation of ubiquitinated protein aggregates, mediated by the macroaggrephagy receptor Cue5.

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.
DOI:10.1038/s44319-024-00275-7
Deficiency in this interaction significantly weakens the association of Cct2 with Atg8.

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.
DOI:10.1016/j.cell.2014.05.048
We thus propose that CUET proteins play a critical and ancient role in autophagic clearance of cytotoxic protein aggregates.

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.
DOI:10.1080/27694127.2023.2236407
Interestingly, Cue5/Tollip, a known autophagy receptor for aggrephagy, is dispensable for this inclusion body autophagy.

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.

Provenance

Identifier source: TraitMech local identifier
Definition source: DOI:10.1080/15548627.2026.2724473

Parent traits (1)

autophagy traitmech:000638

kg-microbe context

No kg-microbe node embedding matched this record in the 2026-04-25 deepwalk.

Discussions and Knowledge Gaps (2)

Open questions attached to this trait. Seeded by just knowledge-gap-scan and curated; see the corpus-wide index.

Review cargo boundaries and qualified process alignment.

CURATION TODO OPEN aggrephagy-scope-and-ibophagy · raised by codex · 2026-10-06

Not yet attached to a section of this record — a curator sets attaches_to (e.g. causal_graphs#some_edge) so the gap shows beside the mechanism it concerns.

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.

Resolve conditional mechanisms and natural exemplars.

KNOWLEDGE GAP OPEN aggrephagy-context-exemplars-and-mechanisms · raised by codex · 2026-10-06

Not yet attached to a section of this record — a curator sets attaches_to (e.g. causal_graphs#some_edge) so the gap shows beside the mechanism it concerns.

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.

Curation history

2026-10-06T16:23:31Z · MINTED_TRAITMECH_ID · codex
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.