i-AAA complex

GO:0031942 · Other · Multiprotein complex · Proposed

Protease complex of the mitochondrial inner membrane whose catalytic residues lie on the intermembrane space side of the inner membrane; involved in mitochondrial protein turnover. Contains a subunit belonging to the AAA family of ATP-dependent metalloproteases. [GO:0031942]

Image (not hosted — CC_BY_NC_SA_4_0): PMC5748973.1 fig3

Biochemical evidence for adaptor-assisted substrate recruitment, not a micrograph or solved structure. Figure 3A-F shows immunoprecipitation and immunoblots of Tom22-HA, Yme1 and adaptors in wild-type and mutant yeast. Panels G-H show native-gel mobility of tagged Mgr1/Mgr3 with SDS-PAGE controls; apparent masses do not establish subunit copy numbers. OTHER · Saccharomyces cerevisiae (NCBITaxon:4932) · Xi Wu, Lanlan Li and Hui Jiang; CC BY-NC-SA 4.0, via PubMed Central. · CC_BY_NC_SA_4_0 · source: PMC PMC5748973.1 fig3 · DOI:10.1083/jcb.201702125

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
Yme1 i-AAA protease	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	YME1, OSD1, YTA11	ATP-dependent proteolytic core with its catalytic domains facing the mitochondrial intermembrane space. `DOI:10.1083/jcb.201702125` Figure 1 and Results: deletion or ATPase/protease inactivation of Yme1 blocks turnover of tested Tom22-HA and Om45-HA substrates. `ComplexPortal:CPX-1655` The exact accession annotates YME1 as an enzymatic participant, separately from MGR1, MGR3 and zinc.
Mitochondrial inner membrane i-AAA protease complex subunit Mgr1	Protein	part of	`InterPro:IPR013911`	MGR1	Membrane adaptor that contacts substrates and supports their recruitment to Yme1. `DOI:10.1083/jcb.201702125` Figures 3-4: Mgr1 associates with Tom22-HA and contributes to Yme1 recruitment; photo-crosslinking places Mgr1 next to the Tom22 intermembrane-space domain. `InterPro:IPR013911` Issuing-authority entry verifies the Mgr1 family, rather than a generic adaptor domain.
Protein Mrg3-like	Protein	part of	`InterPro:IPR040201`	MGR3, FMP24	Mgr3 membrane adaptor that contacts substrates and cooperates with Mgr1 in recruitment to Yme1. `DOI:10.1083/jcb.201702125` Figures 3-4: Mgr3 supports optimal Tom22 recruitment and crosslinks to its intermembrane-space domain. Both adaptors cooperate; Mgr1 can retain some recruitment without Mgr3. `InterPro:IPR040201` The authority spells the family label Mrg3-like; the reviewed MGR3 protein Q04472 maps to this family. The label is preserved, not interpreted as a different gene.
zinc(2+)	Small molecule	part of	`CHEBI:29105`		Metalloprotease cofactor annotated for the yeast i-AAA complex. `ComplexPortal:CPX-1655` Source participant CHEBI:29105 has the cofactor role; no metal or subunit copy number is supplied.

Source composition assertions

i-AAA complex (ComplexPortal:CPX-1655)

Saccharomyces cerevisiae (NCBITaxon:559292) · ECO:0005547 · retrieved 2026-10-04

Participant	Source type	Source name	Stoichiometry
`UniProtKB:P25573` — Mitochondrial inner membrane i-AAA protease supercomplex subunit MGR1	protein	MGR1	not asserted
`UniProtKB:Q04472` — Mitochondrial inner membrane i-AAA protease supercomplex subunit MGR3	protein	MGR3	not asserted
`UniProtKB:P32795` — Mitochondrial inner membrane i-AAA protease supercomplex subunit YME1	protein	YME1	not asserted
`CHEBI:29105` — zinc(2+)	small molecule	zinc(2+)	not asserted

Curator-scoped import: S288C reference-strain i-AAA composition, not the BY4741/W303 experimental strains or a universal fungal assembly. Source evidence: inferred by curator. The accession was resolved through the Complex Portal accession endpoint; no equivalence xref was inferred.

Taxonomic distribution

NCBITaxon:4932 Saccharomyces cerevisiae — COMMON: Experimentally characterized in laboratory budding yeast; no universal fungal or eukaryotic distribution of the Mgr1/Mgr3-containing assembly is asserted. [DOI:10.1083/jcb.201702125]

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — Table S1 lists BY4741 derivatives for the tagged-substrate turnover and recruitment assays. Photo-crosslinking methods explicitly use W303 derivatives. These experimental strains are not relabeled as S288C. [DOI:10.1083/jcb.201702125]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-strain composition annotation from Complex Portal; distinct from the experimental backgrounds in the 2017 paper. [ComplexPortal:CPX-1655]

Functions

ATP-dependent peptidase activity GO:0004176 — ATP-dependent degradation of selected mitochondrial protein substrates; the curated yeast mechanism includes adaptor-assisted turnover of Tom22 and Om45.
- DOI:10.1083/jcb.201702125 Figure 1 tests tagged substrates using deletion and catalytic mutants. Figure 2 separately measures endogenous Tom22 at 37 C in glucose medium and Om45 at 40 C in respiratory medium. Mgr1/Mgr3 deletion blocks both; yme1 deletion cannot be tested for Om45 at 40 C because it fails to grow. Tags accelerate turnover, and these experiments do not show constitutive degradation of all outer-membrane proteins.

Mechanism graphs

Adaptor-assisted recruitment and degradation of Tom22 (FUNCTION)

Mgr1 and Mgr3 contact the substrate and support recruitment to the Yme1 protease.

Subject	Predicate	Object	Evidence
Mitochondrial inner membrane i-AAA protease complex subunit Mgr1	participates in	Tom22 intermembrane-space domain engaged by adaptors	`DOI:10.1083/jcb.201702125` Figure 4: site-specific photo-crosslinking detects Tom22-Mgr1 products, mainly in the protease-dead background; selected positions also crosslink in wild type.
Protein Mrg3-like	participates in	Tom22 intermembrane-space domain engaged by adaptors	`DOI:10.1083/jcb.201702125` Figure 4: Tom22-Mgr3 photo-crosslinks have a partly different positional pattern from Tom22-Mgr1 products; the assay does not establish an atomic interface.
Tom22 intermembrane-space domain engaged by adaptors	promotes	Tom22 associated with Yme1	`DOI:10.1083/jcb.201702125` Figure 3B-C and F: removing either adaptor reduces substrate association with Yme1. Both optimize recruitment; Mgr1 can bind substrate without Mgr3, so an obligatory simultaneous binding event is not asserted.
Tom22 associated with Yme1	is processed by	i-AAA complex	`DOI:10.1083/jcb.201702125` Figures 1 and 3 jointly support recruitment followed by Yme1-dependent processing: ATPase/protease mutants block turnover and can trap substrate association. This transition is mechanistic interpretation, not direct observation of translocation.
i-AAA complex	promotes	Turnover of tested Tom22 substrate	`DOI:10.1083/jcb.201702125` Figure 1D-F: adaptor deletion, YME1 deletion or catalytic inactivation impairs Tom22-HA turnover. Figure 2I-J separately tests endogenous Tom22 at 37 C in glucose medium; no universal outer-membrane turnover claim follows.

Discussions

CURATION_TODO (OPEN): Resolve an exact whole-protein family grounding for Yme1 without conflating it with FtsH or one domain. Bounded native UniProt/InterPro checks verified IPR005936 as a broader FtsH family and IPR048438 as an N-terminal domain. Neither exactly denotes this component class.
INTERPRETATION (RESOLVED): Separate the adaptor-bearing yeast assembly, protease core and substrate proteins. Substrate binding and catalytic loss of function do not make Tom22 or Om45 constituents or prove that adaptor deletion prevents Yme1 oligomerization.
CURATION_TODO (OPEN): Establish intact adaptor-bearing architecture and physiological substrate range with direct structural and condition-matched evidence. Native-gel migration and trapped photo-crosslinks do not determine stoichiometry or visualize substrate movement. Tagged substrates turn over faster than endogenous proteins, and temperature/media matter. The linked biochemical figure is not a micrograph of the complex. Earlier adaptor papers and the separate Yme1 core structural study require full-text review before extending this record.

Evidence

DOI:10.1083/jcb.201702125 Wu, Li and Jiang (2017), Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45. Main Results/discussion, strain and recruitment/crosslinking methods, Figures 1-4 and Table S1 inspected in checksum-verified PMC5748973 version 1.
GO:0098800 Exact inner mitochondrial membrane protein complex parent; distinct from parthood in the membrane.
GO:0005743 Containing mitochondrial inner membrane; the protease catalytic domains face the intermembrane space.

Curation history

2026-10-04T23:57:39Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-04T23:59:47Z codex · EXPANDED_RECORD — Added yeast-scoped components, source-normalized S288C composition, ATP-dependent function, five evidence-backed mechanistic edges, strain/architecture limitations and a restricted-license link-only biochemical figure.
2026-10-05T00:17:05Z codex · CORRECTED_METADATA — Issue #2043: preserve 1 nonprotein Complex Portal source name(s) in source_name instead of gene_symbol; identities, labels, taxa, membership and stoichiometry unchanged.

Source: data/structures/other/i_aaa_complex.yaml