m-AAA complex

GO:0005745 · Other · Multiprotein complex · Proposed

Protease complex of the mitochondrial inner membrane that is involved in mitochondrial protein turnover and in processing of proteins imported into mitochondria. [GO:0005745]

Image (not hosted — OTHER): PMC13376388.1 Fig4

Figure 4: MrpL32 precursor/mature anti-Strep immunoblots and quantification, followed by yeast serial-dilution growth assays with PHB1 or Yta12-domain perturbations. This is biochemical and growth evidence, not a micrograph or atomic structure. OTHER · Saccharomyces cerevisiae (NCBITaxon:4932) · Dingyi Luo, Lvqin Zheng, Ming-Ao Lu, Ziyao Chen, Panpan Wang, Qiang Guo and Ning Gao; CC BY-NC-ND 4.0, via PubMed Central. · OTHER · source: PMC PMC13376388.1 Fig4 · DOI:10.1038/s41467-026-73040-0

Part of: mitochondrial inner membrane (GO:0005743)

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

Components

Component	Type	Part of / acts on	Grounding	Genes	Role
Yta10-type m-AAA protease subunit	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	AFG3, YTA10	AAA ATPase/metalloprotease subunit class represented by Yta10 in the studied yeast heteromer; catalytic domains face the matrix. `ComplexPortal:CPX-1654` The source assigns reviewed UniProt P39925, primary gene AFG3 and alias YTA10, as an enzymatic participant. `https://www.ebi.ac.uk/emdb/EMD-1712` The deposited yeast preparation contains Yta10 and Yta12. Membership is distinct from an inferred assembly sequence or a universal two-paralog composition.
Yta12-type m-AAA protease subunit	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	YTA12, RCA1	Partner AAA ATPase/metalloprotease subunit class in the studied yeast heteromer; its intermembrane-space region includes the experimentally perturbed SIM segment. `ComplexPortal:CPX-1654` The exact source entry assigns reviewed UniProt P40341 as an enzymatic participant. `DOI:10.1038/s41467-026-73040-0` Figure 4 and yeast engineering methods test endogenous Yta12 SIM or larger IMSD replacements in W303-1B. The processing phenotype does not alone establish defective oligomer assembly.
zinc(2+)	Small molecule	part of	`CHEBI:29105`		Source-annotated metalloprotease cofactor. `ComplexPortal:CPX-1654` CHEBI:29105 is a cofactor participant; no zinc or protein copy number is supplied by Complex Portal.

Source composition assertions

m-AAA protease complex (ComplexPortal:CPX-1654)

Saccharomyces cerevisiae (NCBITaxon:559292) · ECO:0000353 · retrieved 2026-10-05

Participant	Source type	Source name	Stoichiometry
`UniProtKB:P40341` — Mitochondrial inner membrane m-AAA protease component YTA12	protein	YTA12	not asserted
`UniProtKB:P39925` — Mitochondrial inner membrane m-AAA protease component YTA10	protein	AFG3	not asserted
`CHEBI:29105` — zinc(2+)	small molecule	zinc(2+)	not asserted

Curator-scoped import: S288C reference-strain m-AAA composition, separate from W303-1B assays and the EMD-1712 preparation; not a universal eukaryotic assembly. Source evidence: physical interaction evidence. The accession was resolved through the Complex Portal accession endpoint; no equivalence xref was inferred.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — W303-1B-derived endogenous YTA12 domain-replacement and PHB-deletion strains were used for MrpL32 reporter processing and oxidative-stress assays. This is not evidence that the S288C reference strain was used experimentally. [DOI:10.1038/s41467-026-73040-0]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-strain composition annotation. The source's generic species label is preserved within complex_compositions; its numeric taxon denotes S288C, not W303-1B. [ComplexPortal:CPX-1654]

Functions

mitochondrial protein processing GO:0034982 — Proteolytic maturation of mitochondrial precursor proteins; the curated primary assay monitors a C-terminally Strep-tagged MrpL32 reporter in yeast mitochondria.
- DOI:10.1038/s41467-026-73040-0 Figure 4a-b and Methods quantify precursor/total MrpL32 after growth in YPG for 14 h at 30 C, using four biological replicates. This endpoint assay is not a direct measurement of processing rate, endogenous untagged substrate behavior or ribosome incorporation.
ATP-dependent peptidase activity GO:0004176 — ATP-dependent proteolysis by the matrix-facing mitochondrial inner-membrane protease.
- ComplexPortal:CPX-1654 Curated source function identifies an ATP-dependent protease with catalytic domains facing the matrix. The 2026 reporter assay does not independently test ATP dependence.

Mechanism graphs

Yeast m-AAA processing and perturbation responses (REGULATION)

Domain replacements in Yta12 and loss of Phb1 alter MrpL32 reporter maturation and growth under respiratory oxidative stress.

Subject	Predicate	Object	Evidence
m-AAA complex	catalyzes	mitochondrial protein processing	`DOI:10.1038/s41467-026-73040-0` Introduction, Figure 4a-b and MrpL32 processing methods identify the protease and assay its substrate-processing output. Mature and precursor species are distinguished by anti-Strep immunoblotting.
PHB1 deletion	enhances assayed maturation	mitochondrial protein processing	`DOI:10.1038/s41467-026-73040-0` Figure 4a-b: the precursor/total MrpL32 ratio is reduced in the phb1 deletion strain. The authors interpret this as enhanced processing; flux and untagged endogenous protein were not measured here.
Yta12 SIM replaced by a linker	enhances assayed maturation	mitochondrial protein processing	`DOI:10.1038/s41467-026-73040-0` Figure 4a-b and cloning methods: the GGGGGS replacement of residues 236-251 yields a lower precursor/total ratio. This supports SIM-dependent control without directly visualizing a yeast PHB-binding interface.
Yta12 IMSD replaced by a linker	impairs assayed maturation	mitochondrial protein processing	`DOI:10.1038/s41467-026-73040-0` Figure 4a-b: the IMSD replacement raises the precursor/total ratio. Compromised protease assembly is the authors' interpretation, not a directly demonstrated consequence in this assay.
PHB1 deletion	increases	Reduced growth under respiratory peroxide stress	`DOI:10.1038/s41467-026-73040-0` Figure 4c: serial-dilution growth on YPG with 2 mM H2O2 is reduced and partially rescued by PHB1 expression. The corresponding sensitivity is not observed on fermentative YPD in this experiment.
Yta12 SIM replaced by a linker	increases	Reduced growth under respiratory peroxide stress	`DOI:10.1038/s41467-026-73040-0` Figure 4d: compare YPG with and without 2 mM H2O2 and the separate YPD controls; incubation is 3 days on YPG and 2 days on YPD at 30 C.
Yta12 IMSD replaced by a linker	increases	Reduced growth under respiratory peroxide stress	`DOI:10.1038/s41467-026-73040-0` Figure 4d: impaired growth under peroxide is distinct from basal viability on YPG. This is not equivalent to deletion of the entire YTA12 gene.

Discussions

CURATION_TODO (OPEN): Resolve separate exact whole-protein family identities for Yta10-type and Yta12-type subunits. Native reviewed UniProt and InterPro checks resolve shared ATP-dependent Zinc Metalloprotease IPR050928 and broader FtsH IPR005936 families; IPR011546 is a domain. These do not distinguish the Yta10 and Yta12 paralog classes, so no broad family or domain is asserted as exact identity.
INTERPRETATION (RESOLVED): Distinguish the m-AAA protease from its substrate and the larger prohibitin-protease association. The same 2026 study combines yeast reporter genetics, C. thermophilum heterologous purification, predicted interfaces and human in situ imaging. Treating all as one endogenous yeast structure would conflate species, preparations and entity boundaries.
CURATION_TODO (OPEN): Resolve native yeast architecture and context-specific stoichiometry from fully read primary structural evidence. EMD-1712 represents a cross-linked detergent sample with C6 symmetry and reported 3:3 subunit counts. Complex Portal leaves copy counts unspecified and lists 1000 kDa, whereas EMDB lists 0.5 MDa for its sample. These source annotations are not reconciled as one physiological mass or fixed family-wide stoichiometry.
CURATION_TODO (OPEN): Test endogenous substrate processing and the causal route from protease regulation to respiratory peroxide sensitivity. The 2026 processing assay uses a TEF-driven C-terminal Strep reporter and endpoint precursor fractions. Domain replacements can affect more than one molecular property, and growth is a distinct assay. Neither reporter changes nor growth phenotypes alone prove assembly failure, general proteome hyperdegradation or a direct MrpL32-to-stress mechanism.

Datasets

Three-dimensional CryoEM Structure of a Membrane-Anchored AAA Protease (EMDB:EMD-1712) · OTHER · STRUCTURAL_IMAGING
Organism: Saccharomyces cerevisiae (NCBITaxon:4932) · Platform: Single-particle cryo-EM; JEOL 2010F
Depositor metadata describes a Yta10/Yta12 heterohexamer with three copies of each and 12 angstrom reconstruction resolution. These are sample/model annotations, not universal canonical copy counts or a resolved alternating paralog arrangement.
Full native XML SHA-256 723a9513e5b5082264156a59e0bfd49f7e168af9596506a9a0d286446fca0ad4. The entry supersedes EMD-1543. No strain or mutation details absent from the header are filled from search snippets. Resolution and map box dimensions are not biological physical properties; no map or image is hosted.
- https://www.ebi.ac.uk/emdb/EMD-1712 Natural source is taxon 4932. Header records sample composition, cross-linking, detergent/ATP conditions and reconstruction symmetry; it does not specify a wild-type physiological structure.

Evidence

DOI:10.1038/s41467-026-73040-0 Luo and colleagues (2026), Structural basis for prohibitin-mediated regulation of mitochondrial m-AAA protease. Introduction, relevant Results, Discussion, yeast engineering/processing/stress methods and Figures 3-4 inspected in PMC13376388.1; the record uses the yeast experiments, not human in situ imaging as yeast evidence.
https://www.ebi.ac.uk/emdb/EMD-1712 Native released EMDB entry and complete XML header inspected; primary citation metadata matches PMID:21147776 / DOI:10.1074/jbc.M110.158741. The full 2011 article was not accessible through attempted routes, so claims here are limited to directly inspected archive metadata.
GO:0098800 Native GO/OAK hierarchy places the complex under inner mitochondrial membrane protein complex, whose membrane parthood is inherited.
GO:1905368 A second verified is-a parent is peptidase complex.

Curation history

2026-10-05T00:59:44Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T01:02:24Z codex · EXPANDED_RECORD — Added yeast-scoped subunit classes, normalized source composition, processing and ATP-dependent functions, seven intervention-bounded mechanistic edges, native structural-dataset provenance and a link-only restricted-license figure.

Source: data/structures/other/m_aaa_complex.yaml