| Property | Description | Evidence Source |
|---|---|---|
| Protein identity | **tomm-22 / W10D9.5** in *Caenorhabditis elegans* is annotated as a homolog of **Tom22**, a subunit of the translocase of the outer mitochondrial membrane (TOM) complex; recent worm work explicitly describes TOMM-22 as being involved in protein transport across the outer mitochondrial membrane. | (pqac-00000036, pqac-00000035) |
| Molecular function | Tom22 is a **mitochondrial preprotein import receptor** and organizer of the TOM complex. Its cytosolic domain binds positively charged mitochondrial targeting presequences, complementing Tom20 by recognizing the more hydrophilic face of amphipathic presequences; it then helps transfer precursor proteins toward the Tom40 channel. | (pqac-00000000, pqac-00000002, pqac-00000046) |
| Subcellular localization | Tom22 is a **single-pass outer mitochondrial membrane protein** with the **N-terminus exposed to the cytosol** and the **C-terminus exposed to the intermembrane space (IMS)**, placing it on both sides of the import pathway. | (pqac-00000001, pqac-00000002, pqac-00000009) |
| Domain architecture | Tom22 contains three major regions: **(1) N-terminal cytosolic receptor/cis domain**, often acidic and presequence-binding; **(2) one transmembrane helix** anchoring it in the outer membrane; and **(3) a C-terminal IMS/trans domain** involved in trans-site binding and transfer to downstream machinery. Human structural work further resolves acidic and amphipathic sequence features in the cytosolic region that support preprotein binding. | (pqac-00000001, pqac-00000002, pqac-00000029) |
| Structural role in TOM complex | Tom22 is a **central structural organizer** of the TOM core complex. Biochemical and structural studies show it associates tightly with Tom40 and small Tom proteins, and cryo-EM indicates **two Tom22 molecules bridge/tether the two Tom40 β-barrels** in the dimeric complex, helping stabilize higher-order TOM architecture. | (pqac-00000004, pqac-00000008, pqac-00000010, pqac-00000030) |
| Role in precursor transfer | Tom22 participates in a **chain of low-affinity binding and handoff steps**: presequences are recognized by Tom20/Tom22 at the cytosolic face, passed toward **Tom5/Tom40**, and then encounter a **trans site** formed by IMS-exposed regions of Tom22, Tom40, and Tom7. | (pqac-00000003, pqac-00000044, pqac-00000046, pqac-00000047) |
| Coupling to TIM23 pathway | The **IMS domain of Tom22** helps connect TOM to the **TIM23** machinery. It contributes to the trans-site for presequence binding and directly or indirectly recruits **Tim50/Tim23/Tim21**, enabling efficient handoff of presequence-containing substrates into the inner-membrane import pathway. | (pqac-00000003, pqac-00000011, pqac-00000042, pqac-00000043, pqac-00000045) |
| Substrate specificity / what it transports | TOMM-22 is **not an enzyme**; it functions as a receptor/organizer for **nuclear-encoded mitochondrial precursor proteins**, especially those carrying **N-terminal cleavable presequences**. Its binding preference is shaped by electrostatic recognition of positively charged targeting signals. | (pqac-00000000, pqac-00000001, pqac-00000002) |
| Role in UPRmt | In *C. elegans*, **tomm-22 knockdown activates the mitochondrial unfolded protein response (UPRmt)**, as shown by induction of mitochondrial stress reporters. More broadly, TOM/TIM import impairment reduces mitochondrial import efficiency, allowing **ATFS-1** to escape mitochondrial import/degradation and activate the nuclear UPRmt program. UPRmt activation can also upregulate import machinery, including tomm-22. | (pqac-00000016, pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000039) |
| C. elegans RNAi phenotypes | **tomm-22(RNAi)** causes a **DAF-28/insulin secretion defect** and robust UPRmt activation, but unlike **tomm-40** depletion it does **not** cause strong larval arrest or sterility in the cited study, suggesting TOMM-22 is important for mitochondrial homeostasis yet less limiting than TOMM-40 under those RNAi conditions. | (pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000035) |
| Lifespan / stress phenotypes in worms | A genome-wide worm RNAi screen identified **tomm-22** as a UPRmt-inducing gene; in that dataset, **tomm-22(RNAi)** significantly **reduced mean lifespan by 14.5%** relative to empty-vector control. A later study used tomm-22 RNAi as a constitutive UPRmt model with shortened lifespan that could be extended by metformin treatment. | (pqac-00000039, pqac-00000036) |
| Pathway involvement | TOMM-22 functions in **mitochondrial protein import and biogenesis**, specifically the **TOM complex / presequence pathway**, and in worms its perturbation intersects with **mitochondrial stress signaling (UPRmt)** and **DAF-28/insulin secretion physiology**. | (pqac-00000035, pqac-00000042, pqac-00000044) |
| Evolutionary/functional inference confidence | Direct *C. elegans* mechanistic data on TOMM-22 are limited, but confidence in functional annotation is strengthened by strong **family conservation** across fungi, animals, and humans, plus consistent worm RNAi phenotypes tied to mitochondrial import stress. | (pqac-00000035, pqac-00000008, pqac-00000029) |


*Table: This table summarizes the best-supported functional properties of *C. elegans* TOMM-22/W10D9.5, combining direct worm evidence with conserved mechanistic evidence from TOM22 homologs. It is useful for functional annotation because it distinguishes experimentally observed worm phenotypes from higher-confidence family-based inferences about mitochondrial protein import.*