age-associated protein deposit

cellstructuremech:age_associated_protein_deposit · Inclusion · Inclusion body · Proposed

An aging-associated protein inclusion characterized in budding yeast that collects aggregation-prone proteins, usually persists as a single ER-associated deposit, and is preferentially retained in the mother-cell lineage. [DOI:10.1016/j.cub.2017.01.069]

Age-associated deposit formation in budding yeast. Panel A follows Hsp42-GFP and Hsp104-mCherry recruitment; B-C compare wild type and separate chaperone deletions. D-F follow Hsp104 and Hsp42 overexpression and focus growth. Arrows mark deposits; microscopy scale bars are 5 micrometers. Panel G is the authors' assembly model, not an additional micrograph. FLUORESCENCE · *Saccharomyces cerevisiae* (`NCBITaxon:4932`) · Juha Saarikangas and Yves Barral (2015), Figure 6; CC BY 4.0, via PubMed Central. Unmodified. · CC_BY_4_0 · source: PMC PMC4635334.1 fig6 · `DOI:10.7554/eLife.06197`

Synonyms: Agepod; APOD; age-associated protein deposit site

UniProt location names: UniProt Consortium, CC BY 4.0. Reference label and route sources.

Components

Component	Type	Part of / acts on	Grounding	Genes	Essential	Role
heterogeneous age-associated protein cargo	Other	part of	Reviewed label only (reviewed name; no accession asserted)		UNKNOWN	Protein material collected into a persistent aging-associated inclusion. The complete native inventory is unresolved; the conditional Sup35 example below is part of this cargo, not an additional fixed layer. `DOI:10.7554/eLife.06197` Results on early replicative aging and Figures 1-2 establish persistent protein deposition and conditional Sup35 recruitment. `DOI:10.1016/j.cub.2017.01.069` Discussion explicitly leaves the full constituent inventory unresolved.
Small heat shock protein	Protein	part of	`InterPro:IPR031107`	HSP42, HSP26	CONDITIONAL	Deposited chaperone class represented by Hsp42 and conditionally Hsp26. Hsp42 appears before Hsp104 and promotes collection into the normal deposit. Hsp26 enrichment occurs in only 15% of assayed deposits; its deletion does not abolish deposition. The formation requirement applies to Hsp42 in the tested assay, not to every family member. `DOI:10.7554/eLife.06197` Results and Figures 1C, 6-7 distinguish collection by Hsp42 from Hsp26 association and mutant phenotypes. `InterPro:IPR031107` Native family metadata and complete three-entry integrated match sets for both examples verify the family; domains are not substituted for it.
Hsp104-type disaggregase	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	HSP104	DISPENSABLE	Deposit-associated disaggregase and experimental marker. HSP104 deletion accelerates Ssa1-marked deposit formation, while overexpression suppresses or destabilizes deposits. Hsp104 positivity alone does not identify every focus as Agepod. `DOI:10.7554/eLife.06197` Figures 6-7 use different reporters to distinguish Hsp104 marker loss from loss of the deposit. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P31539/?page_size=200` Complete native match set checked through next=null.
Heat shock protein 70 family	Protein	acts on	`InterPro:IPR013126`	SSA1, SSA2	UNKNOWN	Associated chaperone family represented by Ssa1 and Ssa2. Each single deletion accelerates Hsp104-focus accumulation; this does not establish dispensability of the whole family or a combined-deletion phenotype. `DOI:10.7554/eLife.06197` Figure 1C and inspected Figure 6C support localized examples and distinguish the single deletions. `InterPro:IPR013126` Native family metadata and both complete five-entry match sets verify membership. The generic family label does not assert residence of every Hsp70 paralog.
Ydj1-type Hsp40 cochaperone	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	YDJ1	UNKNOWN	Conditionally deposit-enriched cochaperone, not a universal deposit coat. Farnesylatable N-terminal GFP-Ydj1 is enriched in only 9.4% of Hsp104 deposits. Its better-supported upstream role in precursor confinement does not establish that it tethers the assembled deposit. `DOI:10.1016/j.cub.2017.01.069` Results and Supplemental Figure S5A contrast functional farnesylation with C-terminal tagging; S5D-E show preserved ER apposition after YDJ1-C406S. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P25491/?page_size=200` Complete native match set checked through next=null.
Eukaryotic peptide chain release factor GTP-binding subunit	Protein	part of	`InterPro:IPR003285`	SUP35	UNKNOWN	Conditional cargo represented by prion-converted Sup35, enriched in approximately one third of assayed deposits in [PSI+] cells but not in the tested [psi-] cells. This is a subset of heterogeneous cargo, not a universal component or proof that Sup35 prions initiate the structure. `DOI:10.7554/eLife.06197` Figure 2 reports conditional Sup35 deposition and mother retention; prion state did not potentiate overall deposit formation. `InterPro:IPR003285` Native family definition and the complete nine-entry P05453 match set verify this exact generic family. The accession denotes the protein class, not its prion conformation.

Organism-specific protein examples

Named proteins in which each component's role was established, with the organism the evidence comes from. The component above is the taxon-agnostic family; these are the specific entries behind it.

Small heat shock protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:Q12329`	Heat shock protein 42	HSP42	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of all experimental backgrounds to S288C. Figures 1C and 6 show deposit association, earlier Hsp42 recruitment and suppressed normal deposition after HSP42 deletion. `UniProtKB:Q12329` Native reviewed entry verifies accession, protein name, gene and reference taxon. `DOI:10.7554/eLife.06197` Figures 1C and 6 show deposit association, earlier Hsp42 recruitment and suppressed normal deposition after HSP42 deletion.
`UniProtKB:P15992`	Heat shock protein 26	HSP26	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of all experimental backgrounds to S288C. Figure 1C reports enrichment in a minority of deposits; inspected Figure 6C shows increased, not abolished, foci after HSP26 deletion. `UniProtKB:P15992` Native reviewed entry verifies accession, protein name, gene and reference taxon. `DOI:10.7554/eLife.06197` Figure 1C reports enrichment in a minority of deposits; inspected Figure 6C shows increased, not abolished, foci after HSP26 deletion.

Hsp104-type disaggregase

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P31539`	Heat shock protein 104	HSP104	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of all experimental backgrounds to S288C. Figures 1, 6 and 7 establish association and show that the structure can form without Hsp104. `UniProtKB:P31539` Native reviewed entry verifies accession, protein name, gene and reference taxon. `DOI:10.7554/eLife.06197` Figures 1, 6 and 7 establish association and show that the structure can form without Hsp104.

Heat shock protein 70 family

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P10591`	Heat shock protein SSA1	SSA1	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of all experimental backgrounds to S288C. Figure 1C supports deposit association; Figure 6C labels a separate ssa1 deletion group. `UniProtKB:P10591` Native reviewed entry verifies accession, protein name, gene and reference taxon. `DOI:10.7554/eLife.06197` Figure 1C supports deposit association; Figure 6C labels a separate ssa1 deletion group.
`UniProtKB:P10592`	Heat shock protein SSA2	SSA2	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of all experimental backgrounds to S288C. Figure 1C supports deposit association; Figure 6C labels a separate ssa2 deletion group. `UniProtKB:P10592` Native reviewed entry verifies accession, protein name, gene and reference taxon. `DOI:10.7554/eLife.06197` Figure 1C supports deposit association; Figure 6C labels a separate ssa2 deletion group.

Ydj1-type Hsp40 cochaperone

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P25491`	Mitochondrial protein import protein MAS5	YDJ1	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of all experimental backgrounds to S288C. Inspected Supplemental Figure S5A shows conditional enrichment of N-terminal GFP-Ydj1. The native UniProt recommended name is retained without implying a mitochondrial location for Agepod. `UniProtKB:P25491` Native reviewed entry verifies accession, protein name, gene and reference taxon. `DOI:10.1016/j.cub.2017.01.069` Inspected Supplemental Figure S5A shows conditional enrichment of N-terminal GFP-Ydj1. The native UniProt recommended name is retained without implying a mitochondrial location for Agepod.

Eukaryotic peptide chain release factor GTP-binding subunit

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P05453`	Eukaryotic peptide chain release factor GTP-binding subunit	SUP35	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of all experimental backgrounds to S288C. Figure 2 distinguishes [PSI+] cargo recruitment from the absence of enrichment in the non-prion state. `UniProtKB:P05453` Native reviewed entry verifies accession, protein name, gene and reference taxon. `DOI:10.7554/eLife.06197` Figure 2 distinguishes [PSI+] cargo recruitment from the absence of enrichment in the non-prion state.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — Species-level experimental scope for localization, inheritance and precursor-confinement assays. The accepted manuscript includes a strain/genotype table; no finer strain identity is inferred from genotype resemblance. [DOI:10.1016/j.cub.2017.01.069]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Figure 1 supplement 2 explicitly describes S288C-background deposition, alongside W303 experiments. This is also the native reference taxon for the reviewed protein examples; not every assay or hosted panel is reassigned to it. [DOI:10.7554/eLife.06197]
NCBITaxon:1247190 Saccharomyces cerevisiae BY4741 — Methods identifies BY4741 derivatives for the mTOR study. Its aging Hsp104-focus readout is operational and does not independently resolve every focus against INQ or other deposits. Native NCBI taxonomy verifies the strain ID. [DOI:10.1016/j.jbc.2025.108172]

Functions

collection of aggregation-prone protein material — Concentrates selected protein cargo into an aging-associated deposit, typically one persistent focus after initial formation. This is not an exhaustive cargo inventory or proof of a fixed material state.
- DOI:10.7554/eLife.06197 Figures 1-2 and 6-7 support persistent collection and chaperone-dependent organization.
asymmetric retention of deposited protein material — Preferentially retains assembled deposits in mother cells during division. Retention of the visible deposit and confinement of its proposed smaller precursors are distinct mechanisms.
- DOI:10.7554/eLife.06197 Figures 1F and 2G measure mother retention of Hsp104- and Sup35-marked deposits.
- DOI:10.1016/j.cub.2017.01.069 Figures 3-4 distinguish mature-deposit passage from new deposit formation in daughters.

Mechanism graphs

Chaperone-dependent deposition and deposit merger (ASSEMBLY)

Subject	Predicate	Object	Evidence
HSP42 deletion	suppresses	age-associated protein deposit	`DOI:10.7554/eLife.06197` Figures 6B-C and 7A-C.
HSP104 deletion	accelerates formation of	age-associated protein deposit	`DOI:10.7554/eLife.06197` Figure 7A-B.
Hsp42 overexpression	promotes formation of	age-associated protein deposit	`DOI:10.7554/eLife.06197` Inspected Figure 6D-F.
Hsp104 overexpression	suppresses accumulation of	age-associated protein deposit	`DOI:10.7554/eLife.06197` Inspected Figure 6D-E and Results.
SSA1 deletion	accelerates accumulation of	age-associated protein deposit	`DOI:10.7554/eLife.06197` Inspected Figure 6C; not a double deletion.
SSA2 deletion	accelerates accumulation of	age-associated protein deposit	`DOI:10.7554/eLife.06197` Inspected Figure 6C; not a double deletion.
age-associated protein deposit	can undergo	Merger of pre-existing deposits after mating	`DOI:10.1016/j.cub.2017.01.069` Figure 2 and associated Results.
PRM3 deletion in both mating partners	impairs	Merger of pre-existing deposits after mating	`DOI:10.1016/j.cub.2017.01.069` Figure 2H-L and Results.

Deposit appearance in daughters versus mature-deposit retention (FUNCTION)

Subject	Predicate	Object	Evidence
BUD1 deletion	increases	New stable deposit formation in daughter cells	`DOI:10.1016/j.cub.2017.01.069` Inspected Figure 3B-C and Results.
SUR2 deletion	increases	New stable deposit formation in daughter cells	`DOI:10.1016/j.cub.2017.01.069` Inspected Figure 3B-C.
BUD6 deletion	increases	New stable deposit formation in daughter cells	`DOI:10.1016/j.cub.2017.01.069` Inspected Figure 3B-C and Results.
YDJ1-C406S farnesylation-site mutation	increases	New stable deposit formation in daughter cells	`DOI:10.1016/j.cub.2017.01.069` Inspected Figure 4D-F.
YDJ1-C406S farnesylation-site mutation	does not detectably impair	Mother retention of pre-existing deposits	`DOI:10.1016/j.cub.2017.01.069` Inspected Figure 4C and Supplemental Figure S5D-E.

mTOR-pathway perturbations of aging-associated foci (REGULATION)

Subject	Predicate	Object	Evidence
NPR3 deletion	increases and advances	Hsp104 foci during replicative aging	`DOI:10.1016/j.jbc.2025.108172` Aging Results and Figure 4.
TCO89 deletion	reduces	Hsp104 foci during replicative aging	`DOI:10.1016/j.jbc.2025.108172` Aging Results and Figure 4; not the discordant original heat-screen hit.

Age-dependent persistence under aggregation-modifying treatments (DISASSEMBLY)

Subject	Predicate	Object	Evidence
Rapamycin treatment of younger cells	reduces	Younger-cell Hsp104 foci	`DOI:10.1016/j.jbc.2025.108172` Figure 5A and aging Results.
Cycloheximide treatment of younger cells	reduces	Younger-cell Hsp104 foci	`DOI:10.1016/j.jbc.2025.108172` Figure 5A and Methods.
Rapamycin treatment of older cells	does not clear	Older-cell persistent Hsp104 deposits	`DOI:10.1016/j.jbc.2025.108172` Figure 5B and aging Results.

Discussions

INTERPRETATION (RESOLVED): Keep the aging-defined deposit distinct without imposing a universal compartment topology. Shared markers and perinuclear proximity do not establish exact identity.
CURATION_TODO (OPEN): Resolve exact source-neutral groundings for heterogeneous cargo and narrow Hsp104/Ydj1 classes. Broader chaperone families and variable client inventories are not exact identities.
INTERPRETATION (RESOLVED): Separate conditional Ydj1 residence from the proposed precursor-confinement mechanism. Fluorescent tag placement changes farnesylation and exchange; diffusion is not direct client identification.
INTERPRETATION (RESOLVED): Do not convert upstream factors, marker negatives or lifespan correlations into composition and universal function. Localization, genetic dependence and pleiotropic phenotypes answer different questions.
INTERPRETATION (RESOLVED): Preserve single-deletion, tag, dose and assay-context distinctions. A source inconsistency or readout boundary must not be flattened into a stronger claim.
CURATION_TODO (OPEN): Resolve complete native cargo, material state, prevalence and the relationship to nuclear inclusions. A few yeast backgrounds and fluorescence assays do not establish fixed composition, dimensions or lineage-wide presence.

Evidence

DOI:10.7554/eLife.06197 Saarikangas and Barral (2015), PMID 26544680, PMC4635334.1. Native current metadata/JATS verified, not retracted. Read main Results, Discussion, Methods and figure captions; inspected Figure 6. The supplemental strain workbook, videos and raw data were not inspected.
DOI:10.1016/j.cub.2017.01.069 Saarikangas et al. (2017), PMID 28262489. Read the institutional accepted-manuscript PDF including main Results, Discussion, Methods, figure legends and supplemental strain/procedure text. Inspected main Figures 1, 3, 4 and Supplemental Figures S1 and S5. Raw data and movie were not inspected; no reuse licence is inferred for this PDF.
DOI:10.1016/j.jbc.2025.108172 2025 mTOR study, PMID 39798875, PMC11849620.1. Native current metadata/JATS verified, not retracted. Read main Results, aging methods and Data availability; captions inspected but figure pixels and supplemental datasets not independently inspected.
DOI:10.3389/fnmol.2018.00249 2018 spatial protein-quality-control review, PMID 30083092, PMC6064742.1. Native metadata and Figure 1 caption verified for APOD and expanded-name synonyms only; not used as primary mechanistic evidence.
GO:0016234 Native QuickGO verifies active inclusion body as a broader cellular-component parent.

Curation history

2026-10-05T10:03:31Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T10:06:34Z codex · EXPANDED_RECORD — Added bounded Agepod identity and topology, six component classes, seven reference proteins, four intervention graphs, source-limit discussions and an inspected CC BY 4.0 figure.

Source: data/structures/inclusion/age_associated_protein_deposit.yaml