MICOS10 (MIC10, MINOS1, C1orf151) review notes

2026-10-08 session (claude-code, MICROPROTEINS Tier 4)

UniProt Q5TGZ0 (MIC10_HUMAN), 78 aa, canonical protein-coding gene (HGNC:32068). Not an
alternative-ORF peptide: it is the primary ORF of its own locus. Initiator Met removed,
Ser2 N-acetylated (large-scale proteomics, UniProt FT). Isoform 2 (Q5TGZ0-2) is 24 aa,
ending after the first transmembrane segment (VSP_042062/3), and is unlikely to be functional.
Sequence inspection (UniProt SQ): both hydrophobic segments carry a glycine-rich motif,
TM1 IGTGFGLGIV and TM2 AFGSGMGLGMA, and the inter-TM loop is basic (FFKRRMWP),
matching yeast Mic10 (Q96VH5: MGFGVGVF, GIGFGVGRG, FFKRRAFP). These are the motifs
shown in yeast to drive Mic10 oligomerisation and membrane bending and inner-membrane
targeting [PMID:25955210 "Both transmembrane segments of Mic10 carry a characteristic
four-glycine motif"; "targeting of Mic10 to the mitochondrial inner membrane requires a
positively charged internal loop"].

Integral inner membrane protein, C terminus in IMS PMID:22114354.
In human mitofilin complexes with MIC60, MIC19, HSPA9 and outer membrane SAMM50/MTX1/MTX2
PMID:22114354.
Complexome profiling places MICOS subunits in MICOS, a membrane bridging subcomplex with
SAMM50/MTX2/MTX3, and the full MIB complex [PMID:26477565, abstract only]. GOA's
SAM complex HDA row from this paper is a projection of MIB co-migration onto an
outer-membrane complex; the sibling reviews of APOO and APOOL already REMOVE the same row.
MIC13/QIL1 is required to incorporate MIC10 into mature MICOS PMID:25997101; MIC10 and MIC13 stabilise one another PMID:27479602.
Integrative structure (preprint) of human MIC60-MIC19-MIC10-MIC13 PMID:42539326; only the
MIC10 homodimer was a confident homo-oligomer AF3 prediction.

Yeast Mic10 bends membranes in vitro via GxGxGxG-dependent oligomerisation
PMID:25955211,
abstract only. Simulation work on the MIC10 subcomplex supports cardiolipin-assisted
oligomerisation and curvature stabilisation PMID:42647630.
Yeast Mic10 also binds dimeric ATP synthase PMID:28315355; not tested in human in the
cached literature, so not proposed.
Human knockouts: MIC10-KO HeLa cells lose lamellar cristae and have >70 % fewer crista
junctions; remaining CJs are wider; cristae become tube-like/onion-like PMID:32567732. Note this paper argues the
MIC60 subcomplex, not MIC10, is necessary for CJ formation per se, and that MIC10 shapes
lamellar cristae. PMID:33130824 Mic10 KO HeLa: loss of CJs, spherical/onion-like cristae,
reduced crista dynamics.
Disease: biallelic MICOS10 variants (exon-1 deletion + p.Cys58Ser) in a hepatocerebral
mtDNA depletion syndrome; MIC10 protein lost in fibroblasts, cristae and respiration rescued
by re-expression PMID:39510533.

Bare protein binding (7 rows): REMOVE. Koob 2015 (MIC60/MIC26/MIC27) and ARMC1 are
genuine MICOS/MIB associations already captured by complex CC terms; HuRI Y2H partners
MPC2, APOC4, CIDEB have no supported functional context.
SAM complex HDA: REMOVE (wrong membrane; MIB complex row captures the evidence).
All mitochondrion/inner membrane/MICOS/MIB/crista junction/cristae formation rows: ACCEPT.
NEW: GO:0180020 membrane bending activity by ISS from yeast Mic10 (Q96VH5). SGD carries
the BP GO:0097753 membrane bending (IDA, PMID:25955211) on yeast MIC10; the MF term is
newer and is used for OPA1, CHMP2A/CHMP3 etc. Participation test: MF, the protein itself
bends the membrane, so it passes. Human-specific in vitro bending has not been shown.

STREMI, the SLC35A4 uORF microprotein, is reported to share topology and motifs with MIC10
and to regulate cristae morphogenesis (PMID:42069946, not cached; abstract read via
E-utilities only). Relevant to the SLC35A4 alt-ORF review, not used here.