UniProt: O17287 (TOM22_CAEEL) · WormBase: WBGene00021133 · ORF: W10D9.5 · Chromosome II
Gene family: Tom22 (InterPro IPR005683; Pfam PF04281; PANTHER PTHR12504) · 109 aa
Deep research: falcon provider succeeded (tomm-22-deep-research-falcon.md, 41 citations,
Edison "Literature" model, 872 s). The perplexity-lite fallback failed (401 quota) but was
not needed. The falcon report is high quality and surfaced the key worm-genetic and
structural literature used below.
TOMM-22 is the C. elegans ortholog of TOM22, a conserved, small single-pass integral
protein of the mitochondrial outer membrane and a central receptor/scaffold subunit of
the TOM complex (translocase of the outer mitochondrial membrane). The TOM complex is
the main entry gate through which the ~99% of mitochondrial proteins that are
nucleus-encoded and made on cytosolic ribosomes are imported into the organelle.
Topology (UniProt, by similarity to human Q9NS69): cytoplasmic 1–60, transmembrane helix
61–77, intermembrane-space (IMS) tail 78–109. This is the canonical TOM22 architecture: an
N-terminal cytosolic receptor domain, a single TM anchor, and a C-terminal IMS domain.
UniProt curated FUNCTION (O17287): "Central receptor component of the translocase of the
outer membrane of mitochondria (TOM complex) responsible for the recognition and
translocation of cytosolically synthesized mitochondrial preproteins" (By similarity) and
"Together with the peripheral receptor tomm-20 functions as the transit peptide receptor
and facilitates the movement of preproteins into the translocation pore"
[ECO:0000269|PubMed:21264209].
TOMM-40 (the β-barrel) forms the actual conducting pore; TOMM-22 is the receptor/scaffold
that contributes to import but does not itself form the channel. This is why its GOA
molecular-function annotation (GO:0008320) carries the contributes_to qualifier.
All worm data are RNAi/knockdown phenotypes; no biochemical assay of the worm protein and
no characterized null allele exist.
The authors explicitly note how little is known in worm:
PMID:21264209.
Bennett et al. 2014 (PMID:24662282) — genome-scale hsp-6p::gfp UPRmt RNAi screen.
tomm-22 is a UPRmt inducer, classed as a protein-import gene:
PMID:24662282 and grouped with
PMID:24662282. Note the paper's thesis: UPRmt
activation does not predict longevity — lifespan effects of import-gene RNAi are
context-dependent, not a core function.
Xin et al. 2022 (PMID:35608535) — the strongest worm evidence that tomm-22 is
functionally required for import: PMID:35608535. TOM genes are
themselves upregulated during UPRmt as an adaptive response:
PMID:35608535.
Tan et al. 2025 (PMID:40522955) — uses tomm-22(RNAi) as the canonical
"import-associated UPRmt" background for a metformin/aging study. Important for
separating core function from downstream stress phenotype:
PMID:40522955 and
PMID:40522955.
Mechanistic UPRmt link (why an import defect activates UPRmt): the weak-MTS transcription
factor ATFS-1 fails to be imported when TOM/TIM capacity drops and instead goes to the
nucleus (Rolland et al. 2019, PMID:31412237, general mechanism — abstract does not name
tomm-22; treated as background, not tomm-22-specific evidence).
KNOWN (well supported):
- Subunit of the TOM complex / mitochondrial outer membrane translocase complex (family +
UniProt SUBUNIT + worm papers). CORE cellular component.
- Localizes to the mitochondrial outer membrane, single-pass (topology by similarity).
- Functions in protein import into mitochondria; required for import capacity in worm
(Xin 2022). CORE biological process.
- Contributes to the complex's protein-transmembrane-transport activity as a
receptor/scaffold (not the pore). CORE molecular contribution.
- Loss reduces import → activates ATFS-1/UPRmt (hsp-6) and impairs DAF-28/insulin
secretion. These are downstream consequences of the import role, not separate functions.
NOT KNOWN (genuine gaps):
- The worm protein's own biochemistry is unmeasured. Presequence-binding (cis/trans),
chaperone-like activity, and substrate-class specificity are inferred from yeast/human
orthologs; no in vitro or in vivo binding assay of C. elegans TOMM-22 exists. The field
itself flags the paucity of worm data (PMID:21264209). → MF_DARK / residual sub-gap.
- Essentiality is unresolved. Only RNAi (partial) data exist; tomm-22(RNAi) is far
milder than tomm-40(RNAi) and no null/deletion allele has been characterized, so whether
complete loss is lethal in C. elegans is unknown. → BIOLOGY gap.
- Isoforms. Two splice isoforms are annotated: a (O17287-1, full length) and b
(O17287-2, "Missing 1..94" = lacks essentially the entire cytosolic receptor domain and TM
anchor). The existence, expression, and function of isoform b are uncharacterized.
- Lifespan direction is contradictory across studies (Bennett 2014 reports increased
mean lifespan on tomm-22 RNAi; Tan 2025 describes the background as short-lived) — a
pleiotropic/context-dependent readout, explicitly not a core function.
| Term | Aspect | Ev | Decision | Rationale |
|---|---|---|---|---|
| GO:0005742 mito outer membrane translocase complex | CC | IBA | ACCEPT (core) | TOM complex subunit |
| GO:0030150 protein import into mito matrix | BP | IBA | ACCEPT (core) | entry receptor; import required (Xin) |
| GO:0008320 transmembrane protein transporter activity (contributes_to) | MF | IBA | ACCEPT (core, contribution) | receptor/scaffold, not pore — contributes_to correct |
| GO:0005741 mitochondrial outer membrane | CC | IEA | ACCEPT (core) | single-pass OMM |
| GO:0005741 mitochondrial outer membrane | CC | ISS | ACCEPT | same location, ISS from human ortholog |
| GO:0006886 intracellular protein transport | BP | IEA | KEEP_AS_NON_CORE | generic InterPro2GO parent of GO:0030150 |
Core MF for synthesis: GO:0030943 mitochondrion targeting sequence binding (conserved
presequence-receptor activity; the human TOMM22 review uses the same term — note it is
slated for eventual GO obsoletion in favor of a "mitochondrial signal sequence receptor
activity" NTR, but is live as of 2026-05/07).