intramitochondrial protein quality control compartment

cellstructuremech:intramitochondrial_protein_quality_control_compartment · Membrane organelle · Membrane bounded organelle · Proposed

A mitochondrial membrane-enclosed deposit compartment characterized in budding yeast that sequesters aggregated matrix proteins, often near the nucleus and separated from the remaining tubular mitochondrial network. [DOI:10.1242/jcs.263680]

Image (not hosted — OTHER): PMC5996957.1 F1

Reporter constructs, protease protection and fluorescence localization. Destabilized mitochondrial reporter forms deposits; stable controls label the network. Microscopy scale bars: 10 micrometers. FLUORESCENCE · Saccharomyces cerevisiae (NCBITaxon:4932) · Michael Bruderek, Witold Jaworek, Anne Wilkening, Cornelia Rub, Giovanna Cenini, Arion Fortsch, Marc Sylvester and Wolfgang Voos (2018), Figure 1, DOI 10.1091/mbc.E17-01-0027; CC BY-NC-SA 3.0. · OTHER · source: PMC PMC5996957.1 F1 · DOI:10.1091/mbc.E17-01-0027

Synonyms: IMiQ

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
aggregated mitochondrial matrix proteins	Other	part of	Reviewed label only (reviewed name; no accession asserted)			Sequestered misfolded protein material. The destabilized GFP-DHFR reporter is experimental cargo, not an invariant native subunit. `DOI:10.1091/mbc.E17-01-0027` Results and Figures 1-3: targeted destabilized reporter forms sedimentable deposits; endogenous proteins can coaggregate in small, condition-dependent amounts.
Hsp78-type chaperone	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	HSP78	UNKNOWN	Aggregate-associated disaggregase. Recruitment does not demonstrate clearance of the stable IMiQ cargo. `DOI:10.1242/jcs.263680` Figure 4C,E: strong localization at reporter deposits but limited recovery in the sedimentation assay. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P33416/?page_size=200` Native combined InterPro endpoint inspected on 2026-10-05, including all integrated matches (next=null). Family identity is separate from experimental compartment recruitment.
Heat shock protein 70 family	Protein	acts on	`InterPro:IPR013126`	SSC1	UNKNOWN	Aggregate-associated chaperone, exemplified by mitochondrial Ssc1; not a fixed stoichiometric shell in all conditions. `DOI:10.1242/jcs.263680` Figures 4-5: Ssc1 is enriched at deposits; conspicuous rings occur in fis1 deletion cells. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P0CS90/?page_size=200` Native combined InterPro endpoint inspected on 2026-10-05, including all integrated matches (next=null). Family identity is separate from experimental compartment recruitment.

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.

Hsp78-type chaperone

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P33416`	Heat shock protein 78, mitochondrial	HSP78	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence example, not a reassignment of the paper experimental strain. `UniProtKB:P33416` Native reviewed entry verifies the accession, protein name, primary gene and reference taxon. `DOI:10.1242/jcs.263680` Figure 4C,E: strong localization at reporter deposits but limited recovery in the sedimentation assay.

Heat shock protein 70 family

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P0CS90`	Import motor subunit, mitochondrial	SSC1	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reference-sequence example, not a reassignment of the paper experimental strain. `UniProtKB:P0CS90` Native reviewed entry verifies the accession, protein name, primary gene and reference taxon. `DOI:10.1242/jcs.263680` Figures 4-5: Ssc1 is enriched at deposits; conspicuous rings occur in fis1 deletion cells.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — Reporter-defined deposits characterized in budding yeast. Experimental cargo contains mouse DHFR and GFP; those source organisms are not native IMiQ taxa. [DOI:10.1091/mbc.E17-01-0027]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-sequence taxon of the reviewed Hsp78 example, not an assertion that the imaging used S288C. Each other protein example carries its own reviewed accession. [UniProtKB:P33416]

Functions

sequestration of aggregated mitochondrial proteins — Concentrates insoluble matrix protein cargo into a restricted deposit. Preserved growth and import in the tested conditions do not imply universal protection: prolonged reporter expression increased menadione sensitivity and reduced cytochrome b translation.
- DOI:10.1091/mbc.E17-01-0027 Figures 2-4 and Results compare reporter-bearing and control yeast. Functional costs depend on expression duration and stress; aggregation is not equivalent to degradation.
biased retention of mitochondrial aggregate deposits in mother cells — Perinuclear deposits are preferentially retained during budding; daughter-cell inheritance is reduced, not eliminated.
- DOI:10.1091/mbc.E17-01-0027 Figure 5: after reporter induction and shutoff, about 7 percent of daughter cells inherited aggregates, compared with about 98 percent inheriting the control mitochondrial GFP signal.

Mechanism graphs

Reporter-defined IMiQ formation and positioning (ASSEMBLY)

Interventions affecting deposit coalescence, positioning and separation in budding yeast.

Subject	Predicate	Object	Evidence
Expression of mitochondria-targeted destabilized GFP-DHFR	induces	intramitochondrial protein quality control compartment	`DOI:10.1091/mbc.E17-01-0027` Figure 1 contrasts targeted destabilized reporter with stable reporter controls.
intramitochondrial protein quality control compartment	exhibits	Perinuclear localization of mitochondrial reporter deposits	`DOI:10.1091/mbc.E17-01-0027` Figure 5 uses a nuclear marker; positioning is frequent, not invariant.
intramitochondrial protein quality control compartment	exhibits	Separation of aggregate-containing compartments from the tubular network	`DOI:10.1091/mbc.E17-01-0027` Figures 1 and 7 distinguish large deposits from the residual tubular mitochondrial network; separation is not loss of all surrounding membrane.
HSP78 deletion	impairs	Perinuclear localization of mitochondrial reporter deposits	`DOI:10.1091/mbc.E17-01-0027` Figure 7A,C-D: hsp78 deletion cells carry more small network-associated deposits rather than the normal large perinuclear deposit.
FZO1 deletion	impairs	Perinuclear localization of mitochondrial reporter deposits	`DOI:10.1091/mbc.E17-01-0027` Figure 7: fusion-deficient cells show multiple small deposits lacking normal perinuclear coalescence. Respiratory deficiency limits functional interpretation of this strain.
FIS1 deletion	impairs	Separation of aggregate-containing compartments from the tubular network	`DOI:10.1091/mbc.E17-01-0027` Figure 7: aggregate-bearing mitochondrial material remains associated with the hyperconnected network in fis1 deletion cells.
Benomyl treatment	reduces	Perinuclear localization of mitochondrial reporter deposits	`DOI:10.1091/mbc.E17-01-0027` Figure 5: 100 micrograms/ml benomyl for 5 hours reduces perinuclear localization while deposits still form. This pharmacological result does not identify a molecular tether.

Discussions

INTERPRETATION (RESOLVED): Define the membrane-enclosed deposit compartment, rather than its protein cargo alone. A protein aggregate is not equivalent to the entire membrane-enclosed IMiQ compartment. A broader ontology term must not replace the named identity.
CURATION_TODO (OPEN): Resolve whether DUMP and IMiQ represent different states or different structures before merging or splitting their identities. The 2020 DUMP paper explicitly argues distinction from IMiQ based on network localization. The 2025 IMiQ paper instead considers likely similarity or possible identity, while noting functional differences.
CURATION_TODO (OPEN): Resolve exact source-neutral grounding for Hsp78-type chaperones and the heterogeneous aggregate cargo where an appropriate authority supports it. The inspected Hsp78 InterPro matches are broader than the component; the cargo is not one protein family. Exact matches should not be fabricated.
INTERPRETATION (RESOLVED): Distinguish directly localized chaperones from formation factors and potential copurifying cargo. Genetic effects and affinity enrichment alone do not define stable compartment composition. Reading the remaining 2025 Discussion clarified that Hsp60 colocalization could reflect failed precursor folding or coaggregation, rather than action on the assembled deposit.
CURATION_TODO (OPEN): Resolve native prevalence, membrane composition, deposition lifetime and protocol-dependent chaperone recruitment. Artificial reporter induction establishes a structure under specified conditions, not broad taxonomic prevalence or a universal copy number. The 2018 sedimentation results show little stable chaperone association; the 2025 microscopy shows recruitment that can be lost during isolation.
INTERPRETATION (RESOLVED): Locate the HSP78-deletion morphology evidence in the correct primary figure. The initial PR graph note pointed to Figure 6, which measures growth and thermotolerance, rather than Figure 7, which measures deposit organization.

More images

Image (not hosted — OTHER): DOI:10.1242/jcs.263680 Figure 1

Reporter diagrams, immunoblots, immunofluorescence and transmission electron microscopy of yeast controls and reporter-induced deposits; microscopy scale bars: 2 micrometers. OTHER · Saccharomyces cerevisiae (NCBITaxon:4932) · Laura Ruland, Marc Sylvester, Lydia Maus, Hannes Beckert and Wolfgang Voos (2025), Figure 1, DOI 10.1242/jcs.263680; The Company of Biologists User Licence 1.2. · OTHER · source: OTHER DOI:10.1242/jcs.263680 Figure 1 · DOI:10.1242/jcs.263680

Datasets

Mitochondrial reporter aggregate-associated proteome (PXD059828) · PRIDE · PROTEOMICS
Organism: Saccharomyces cerevisiae (NCBITaxon:4932) · Platform: Orbitrap Fusion Lumos LC-MS/MS
Aggregate-associated proteins are not automatically fixed structural subunits.
Native PRIDE metadata verified accession, yeast taxon, publication DOI/PMID, instrument and CC0 dataset licence on 2026-10-05. Raw files were not downloaded or reanalyzed. Dataset CC0 does not license the paper figures.
- https://www.ebi.ac.uk/pride/archive/projects/PXD059828 Project metadata agrees with the publication Data availability statement.

Evidence

DOI:10.1091/mbc.E17-01-0027 Bruderek et al. (2018), PMID 29212875. Read Results, Discussion, figure captions and selected Methods in PMC5996957.1; actual Figure 1 inspected. Supplementary strain tables were not read; strain identity is not inferred from reference-sequence entries.
DOI:10.1242/jcs.263680 Ruland et al. (2025), PMID 40734647. Read publisher Results on ultrastructure and chaperones, Discussion, Methods and Data availability; actual Figure 1 inspected. Supplements and raw proteomics were not reanalyzed. The Methods introduce fission/fusion deletions into YPH499; reference-sequence accessions do not reassign that experimental background.
GO:0043231 Native QuickGO confirms active cellular-component term intracellular membrane-bounded organelle. It is a broader parent, not the exact identity.

Curation history

2026-10-05T04:10:52Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T04:12:44Z codex · EXPANDED_RECORD — Added yeast-scoped IMiQ evidence, recruited chaperone families, bounded intervention graph, verified PRIDE dataset, link-only figures and unresolved DUMP equivalence.
2026-10-05T04:18:14Z codex · REFINED_PROVENANCE — Placed the experimental YPH499 strain note with its primary-paper citation and narrowed the S288C reference example to its cited accession.
2026-10-05T04:35:09Z codex · REVISED_COMPONENT_BOUNDARY — Removed Hsp60 from canonical associated machinery after full Discussion review; retained directly observed association as an unresolved cargo-versus-machinery boundary.
2026-10-05T04:50:09Z codex · CORRECTED_EVIDENCE — Addressed PR 2052 review issue 2053 by correcting the HSP78 graph evidence locator from Figure 6 to Figure 7A,C-D.

Source: data/structures/membrane_organelle/intramitochondrial_protein_quality_control_compartment.yaml