| Property | C. elegans TIN-44 | Yeast Tim44 | Human TIMM44 |
|---|---|---|---|
| Gene name / synonym | **tin-44**; ORF **T09B4.9**; annotated as probable mitochondrial import inner membrane translocase subunit tin-44 (UniProt O02161) (pqac-00000008) | **Tim44**; classic fungal TIM23/PAM motor subunit (pqac-00000005, pqac-00000021) | **TIMM44**; translocase of inner mitochondrial membrane 44 (pqac-00000033, pqac-00000034) |
| UniProt ID | **O02161** (user-provided target identity; consistent with T09B4.9/tin-44 annotation) | Not directly established in gathered evidence | Not directly established in gathered evidence |
| Protein family | **Tim44 family**; inferred metazoan ortholog of mitochondrial import motor scaffold protein (pqac-00000008, pqac-00000027) | Tim44 family; docking/scaffold component of the PAM import motor associated with TIM23 (pqac-00000001, pqac-00000018) | TIMM44/Tim44 family; PAM-associated mitochondrial protein import factor (pqac-00000034, pqac-00000042) |
| Subcellular localization | Mitochondrial inner membrane import machinery; function inferred on the **matrix side of the inner membrane** from orthology and import-related phenotypes (pqac-00000008, pqac-00000027) | **Peripheral inner mitochondrial membrane protein** on the **matrix face**; hydrophilic, membrane-associated, can interact with cardiolipin (pqac-00000005, pqac-00000007, pqac-00000014) | Mitochondrial inner membrane import machinery / mitochondrial fraction; part of PAM/TIM23-associated import system (pqac-00000034, pqac-00000040) |
| Primary function | Likely **scaffold/adaptor for matrix protein import** through TIM23-PAM; required for efficient mitochondrial protein import, and its knockdown activates UPRmt (pqac-00000008, pqac-00000027, pqac-00000030) | **Scaffold/docking protein** that recruits **mtHsp70** and links the **TIM23 channel** to the **PAM motor** to drive ATP-dependent import of presequence-containing proteins into the matrix (pqac-00000000, pqac-00000001, pqac-00000023) | Essential mitochondrial import factor; supports **pre-protein import**, mitochondrial integrity, respiration/ATP production, and in cancer cells supports Akt-mTOR-linked growth programs (pqac-00000034, pqac-00000035, pqac-00000036) |
| Complex membership | Inferred member of the **TIM23/PAM mitochondrial import machinery** in worms (pqac-00000008, pqac-00000027) | Part of **TIM23MOTOR/PAM**; distinguishes matrix-import motor form from TIM23SORT form (pqac-00000017, pqac-00000018, pqac-00000020) | Component of the **PAM complex** associated with TIM23 (pqac-00000034, pqac-00000042) |
| Key interactions | Functional association with mitochondrial import machinery and UPRmt signaling; transcriptionally co-upregulated with import genes such as **timm-23**, **mppa-1**, **mppb-1** during UPRmt (pqac-00000027) | Interacts with **mtHsp70**, **Mge1**, **Tim17**, **Tim23**, **Pam16/Pam18/Pam17**, incoming presequences, and cardiolipin; recruits motor modules to the translocase (pqac-00000002, pqac-00000003, pqac-00000013, pqac-00000015) | Associated with **TIMM23/TIM23**, PAM components, and functionally linked to mitochondrial import and mitophagy signaling; MB-10 binds the **C-terminal domain** of TIMM44 (pqac-00000034, pqac-00000040, pqac-00000042) |
| Loss-of-function phenotype (RNAi / mutant) | **RNAi induces hsp-6p::gfp UPRmt reporter** and in one genome-wide screen increased mean lifespan by **11.1%**; import impairment is consistent with mitochondrial stress signaling (pqac-00000008, pqac-00000025). Reviews also place TIN-44 among import factors whose depletion induces mitochondrial stress and can reduce lifespan in some contexts (pqac-00000012) | **Essential for matrix-targeted protein import**; temperature-sensitive **tim44-804** strongly inhibits import of matrix-destined precursors while sparing inner-membrane sorting, showing a selective motor defect rather than gross TIM23 destruction (pqac-00000004, pqac-00000021) | **Genetic depletion** or pharmacologic blockade (**MB-10/MitoBloCK-10**) causes mitochondrial depolarization, ROS increase, ATP reduction, apoptosis, and strong inhibition of bladder cancer cell growth; PAM sequestration involving TIMM44 can also reduce import and trigger mitophagy (pqac-00000034, pqac-00000039, pqac-00000042) |
| Disease associations | No direct worm disease annotation; chiefly used as a model for mitochondrial import stress and UPRmt biology (pqac-00000008, pqac-00000030) | Not applicable as a human disease gene; chiefly a mechanistic model for mitochondrial import (pqac-00000001, pqac-00000021) | Open Targets reports associations with **neurodegenerative disease**, **Parkinson disease**, **Alzheimer disease**, **multiple sclerosis**, and **lysosomal storage disease**; recent work also implicates TIMM44 as a potential **bladder cancer therapeutic target** (pqac-00000033, pqac-00000034) |


*Table: This table compares key functional properties of C. elegans TIN-44 with its yeast and human orthologs. It highlights the conserved role of Tim44-family proteins in TIM23/PAM-mediated mitochondrial protein import and summarizes organism-specific phenotypes and disease relevance.*