Mic60-Mic19 complex

cellstructuremech:mic60_mic19_complex · Other · Multiprotein complex · Proposed

A heteromeric MICOS subcomplex composed of Mic60 and Mic19 that couples protein assembly to mitochondrial inner-membrane remodeling and crista-junction organization. [DOI:10.1126/sciadv.abo4946]

Mic60 perturbation context in YPH499-derived Saccharomyces cerevisiae, not an image of the isolated Mic60-Mic19 complex. Full Figure 4: affinity purification (a), respiratory growth (b), mitochondrial cryosection TEM of Mic60-ProtA control and mic60 deletion or lipid-binding mutants (c-f; scale bars 500 nm), crista-junction counts (g), and respiratory-complex activities (h-i). Original multipanel figure retained. TEM · *Saccharomyces cerevisiae* (`NCBITaxon:4932`) · Manuel Hessenberger, Ralf M. Zerbes, Heike Rampelt, Séverine Kunz, Audrey H. Xavier, Bettina Purfürst, Hauke Lilie, Nikolaus Pfanner, Martin van der Laan, Oliver Daumke; CC BY, via PubMed Central · CC_BY_4_0 · source: PMC PMC5460017.1 f4 · `DOI:10.1038/ncomms15258`

Synonyms: Mic19-Mic60 subcomplex

Part of: MICOS complex (GO:0061617)

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

Components

Component	Type	Part of / acts on	Grounding	Genes	Stoichiometry	Essential	Role
MICOS complex subunit MIC60	Protein	part of	`InterPro:IPR019133`	MIC60			Membrane-anchored scaffold whose intermembrane-space region binds Mic19 and lipids; its coiled-coil and mitofilin regions contribute oligomerization and membrane-remodeling interfaces. `DOI:10.1038/ncomms15258` Purified Chaetomium thermophilum Mic60 soluble region binds and tubulates Folch liposomes and directly binds Mic19; lipid-binding-site mutations disrupt crista junctions in budding yeast. `DOI:10.1126/sciadv.abo4946` Fungal domain structures and mutational analysis identify Mic60 oligomerization, Mic19-binding and lipid-binding interfaces. Crystal domain constructs are not a full native complex structure. `InterPro:IPR019133` InterPro resolves this accession as a family named MICOS complex subunit MIC60, rather than a generic coiled-coil domain.
MICOS complex subunit Mic19	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	MIC19			CHCH-domain-containing binding partner that promotes Mic60 higher-order assembly and enhances membrane remodeling by the soluble Mic60 region in fungal reconstitution assays. `DOI:10.1038/ncomms15258` Calorimetry establishes direct Mic19-Mic60 binding through the Mic19 CHCH region and Mic60 mitofilin region. Full Mic19 enhances Mic60-dependent liposome tubulation, branching and dye leakage; Mic19 alone does not bind or remodel these liposomes. `DOI:10.1126/sciadv.abo4946` Mic19 promotes higher-order assembly of purified fungal Mic60; interface substitutions impair binding and budding-yeast crista-junction organization.

Taxonomic distribution

NCBITaxon:4932 Saccharomyces cerevisiae — COMMON: Budding-yeast mitochondrial MICOS contains the Mic60-Mic19 subcomplex; the cited experiments use YPH499 derivatives. This species-level assertion does not establish universal presence in fungi or every strain. [DOI:10.1126/sciadv.abo4946]

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — YPH499-derived strains expressing Mic60 or Mic19 interface variants were examined by mitochondrial affinity purification and electron microscopy. These in vivo experiments are distinct from the purified Chaetomium thermophilum proteins used for membrane reconstitution. [DOI:10.1126/sciadv.abo4946]

Functions

cristae formation GO:0042407 — Supports formation and organization of mitochondrial crista junctions through cooperative Mic60-Mic19 assembly and membrane remodeling, within the larger MICOS machinery.
- DOI:10.1038/ncomms15258 Mic60 lipid-binding mutants in YPH499-derived yeast lose normal crista junctions and accumulate detached lamellar cristae; purified fungal Mic19 enhances Mic60-driven membrane deformation.
- DOI:10.1126/sciadv.abo4946 Mic60 oligomerization-interface and Mic60-Mic19 interaction-interface variants impair crista-junction formation in yeast. The complex is not asserted to be sufficient for native crista formation by itself.

Mechanism graphs

Direct binding and cooperative membrane remodeling by fungal Mic60 and Mic19 (FUNCTION)

Purified fungal proteins establish direct interaction, Mic60-dependent lipid recruitment, Mic19-enhanced oligomerization and membrane tubulation.

Subject	Predicate	Object	Evidence
MICOS complex subunit Mic19	directly binds	MICOS complex subunit MIC60	`DOI:10.1038/ncomms15258` Isothermal titration calorimetry and domain deletions establish direct binding; isolated Mic19 coiled-coil region does not bind Mic60. `DOI:10.1126/sciadv.abo4946` Fusion-domain crystal structures and binding-interface substitutions resolve the heteromeric contact.
MICOS complex subunit MIC60	recruits Mic19 into	Lipid-associated Mic60-Mic19 assembly	`DOI:10.1038/ncomms15258` Liposome co-sedimentation detects Mic19 in the presence of Mic60; Mic19 alone does not bind the tested membranes.
MICOS complex subunit Mic19	promotes	Higher-order Mic60-Mic19 assembly	`DOI:10.1126/sciadv.abo4946` Hydrodynamic and cross-linking experiments support Mic19-induced oligomerization, with an inferred tetrameric Mic60 arrangement rather than a universal native copy count.
MICOS complex subunit MIC60	drives	Liposome tubulation and branching	`DOI:10.1038/ncomms15258` Electron microscopy shows tubulation with purified Mic60; deletion of the amphipathic LBS1 region abolishes lipid binding and remodeling.
Lipid-associated Mic60-Mic19 assembly	enhances	Liposome tubulation and branching	`DOI:10.1038/ncomms15258` Figure 3 reconstitution assays compare Mic60 alone with full Mic19 and Mic19 domain constructs. Full Mic19 stimulates membrane deformation; its domains have different effects on dye leakage.

Discussions

CURATION_TODO (OPEN): Establish an exact taxon-agnostic Mic19 family grounding without treating DUF1690 membership as identity. Reviewed yeast Mic19 cross-references a fungal DUF family, but the current family description does not establish equivalence to the complete Mic19 component class. CHCH-domain membership alone is also insufficient.
CURATION_TODO (OPEN): Determine the native microbial complex architecture and copy number, and directly test the proposed crista-junction strut and diffusion-barrier functions. The 2022 structural model combines isolated fungal domains and engineered fusion constructs. The authors explicitly leave the molecular identity of yeast junction-spanning tomographic densities unresolved. Purified-protein oligomerization does not prove one universal native 4:4 assembly.
CURATION_TODO (RESOLVED): Keep the Mic60-Mic19 subcomplex distinct from full MICOS, MIB and experimental expression hosts. Other MICOS subunits and outer-membrane partners occur in the surrounding machinery but are not constituent identities of this two-component subcomplex. Expression in Escherichia coli does not make the complex a bacterial structure.

Evidence

DOI:10.1038/ncomms15258 Hessenberger et al. (2017), Regulated membrane remodeling by Mic60 controls formation of mitochondrial crista junctions. Full Results, Discussion, methods and Figure 4 inspected in checksum-verified PMC5460017 version 1.
DOI:10.1126/sciadv.abo4946 Bock-Bierbaum et al. (2022), Structural insights into crista junction formation by the Mic60-Mic19 complex. Full Results, Discussion and relevant methods inspected in checksum-verified PMC9432830 version 1.
GO:0098800 The local complex is a type of inner mitochondrial membrane protein complex; this broader GO term is not its exact identity.
GO:0061617 MICOS is the containing complex, not an is-a parent or synonym of the two-component subcomplex.

Curation history

2026-10-04T21:48:42Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-04T21:50:14Z codex · EXPANDED_RECORD — Added source-bounded fungal components, yeast scope, cristae-formation function, direct biochemical mechanism and explicit family/native-architecture limitations.
2026-10-04T21:50:36Z pmc_oa · ADD_IMAGE — Added PMC5460017.1 f4; version, CC licence, JATS figure identity and media md5 verified through the PMC OA S3 dataset.

Source: data/structures/other/mic60_mic19_complex.yaml