| 1996 |
Tom7 is an integral membrane subunit of the mitochondrial outer membrane TOM translocase. Deletion of TOM7 inhibits import of the outer membrane protein porin and strongly impairs two-step preprotein import into the mitochondrial interior. Loss of Tom7 stabilizes interactions between receptors Tom20 and Tom22 and the import pore Tom40, indicating Tom7 exerts a destabilizing effect on part of the outer membrane translocase, while Tom6 stabilizes these interactions. Genetic synthetic growth defects of tom7Δ tom20Δ and tom7Δ tom6Δ double mutants confirmed functional relationships between Tom7, Tom20, and Tom6. |
Yeast genetics (deletion mutants, double mutants), blue native PAGE, import assays in vitro, biochemical fractionation |
The EMBO journal |
High |
8641278
|
| 2001 |
Tom6 and Tom7 are subunits of the Neurospora crassa TOM core complex. Cross-linking experiments showed both proteins are in direct contact with Tom40. Precursors of Tom6 and Tom7 insert into the outer membrane in vitro and assemble into authentic TOM complexes; assembly shares a common binding site with the general import pathway and requires the integrity of TOM receptor components. |
Cross-linking in vivo, in vitro import/assembly assays, blue native PAGE, hybrid protein analysis |
The Journal of biological chemistry |
High |
11278536
|
| 2002 |
Tom7 is a tail-anchored protein; the carboxy-terminal 33 amino acids contain the targeting information for the mitochondrial outer membrane. A conserved proline residue within the transmembrane segment is required for efficient targeting of Tom7 to the outer membrane. An equivalent proline residue is important for targeting each of the other three tail-anchored proteins (Tom5, Tom6, Tom22) that associate with Tom40 to form the TOM core. |
Deletion/truncation analysis, mutagenesis of conserved proline, fluorescence microscopy, import assays |
FEBS letters |
Medium |
11943179
|
| 2002 |
Human TOMM7 is imported into mitochondria in a nucleotide-independent manner and is anchored to the outer membrane with its C terminus facing the intermembrane space. Human Tom7 assembles first into an ~120 kDa import intermediate containing Tom40 but lacking receptor components, which is then chased to the stable ~380 kDa TOM complex additionally containing Tom22. Tom22 is rate-limiting for TOM complex formation, as Tom22 overexpression accelerates Tom7 assembly into the 380 kDa complex. |
Import assays in HeLa cell mitochondria, blue native PAGE, supershift analysis with TOM-specific antibodies, Tom22 overexpression |
The Journal of biological chemistry |
High |
12198123
|
| 2006 |
Tom7 functions in an antagonistic manner to Mdm10 in beta-barrel protein biogenesis. Tom7 promotes segregation of Mdm10 from the SAM(holo) complex into a low molecular mass form. Upon deletion of Tom7, the fraction of Mdm10 in the SAM(holo) complex is significantly increased, selectively promoting Tom40 assembly but not porin assembly. |
Yeast genetics (TOM7 deletion), blue native PAGE, in vitro import/assembly assays, co-immunoprecipitation |
The Journal of biological chemistry |
High |
16760475
|
| 2010 |
Tom7 directly interacts with Tom40 through its transmembrane segment and with Mdm10, as shown by site-specific photocross-linking in vivo. Tom7 recruits Mdm10 and enhances its association with the MMM1 complex, thereby regulating the timing of Tom40 release from the TOB/SAM complex for subsequent assembly into the TOM40 complex. Depletion of Tom7 decreased transient accumulation of Tom40 at the TOB complex, while overexpression of Tom7 enhanced it. |
Site-specific photocross-linking in vivo, in vitro import assays, BN-PAGE, Tom7 depletion and overexpression |
The Journal of biological chemistry |
High |
21036907
|
| 2010 |
Tom7 plays an inhibitory role at two distinct steps in TOM complex biogenesis: (1) Tom7 acts antagonistically to Tom5 and Tom6 at an early stage of Tom40 assembly at the SAM complex; (2) Tom7 interacts with free Mdm10 (not bound to the SAM complex), thereby promoting dissociation of the SAM-Mdm10 complex and delaying Tom22 assembly with Tom40 at a late stage. Thus Tom7 modulates biogenesis of both the beta-barrel protein Tom40 and the alpha-helical Tom22. |
Yeast genetics, blue native PAGE, in vitro import assays, co-immunoprecipitation |
Journal of molecular biology |
High |
21059357
|
| 2018 |
Tomm7 deficit in endothelial cells induces increased import of Rac1 protein into mitochondria and facilitates mitochondrial Rac1-coupled redox signaling, causing angiogenic impairment that underlies cerebrovascular network malformation. Endothelial-specific transgenesis of tomm7 restored cerebrovascular anomalies in Tomm7-knockout mice. |
Loss-of-function genetic screening in zebrafish, conditional knockout mice, endothelial-specific transgenesis, vascular imaging, mitochondrial protein import assays |
Arteriosclerosis, thrombosis, and vascular biology |
Medium |
30354240
|
| 2019 |
Tom7 is required for PINK1 accumulation at the outer mitochondrial membrane upon mitochondrial depolarization. Deletion of Tom7 allows PINK1 to be imported into depolarized mitochondria where it is cleaved by the OMA1 protease rather than arrested at the outer membrane. PINK1 contains a negatively charged amino acid cluster motif C-terminal to its transmembrane domain that is required for import arrest; mutagenesis of this motif phenocopies Tom7 deletion. Thus, ΔΨm-loss-dependent PINK1 import arrest involves an actively regulated 'tug of war' between Tom7 (promoting outer membrane retention) and OMA1 (promoting PINK1 cleavage after inner-membrane import). |
Tom7 knockout cell lines, PINK1 mutagenesis, OMA1 suppression, import assays, protease protection assays, cell biology |
Molecular cell |
High |
30733118
|
| 2022 |
A homozygous missense variant in TOMM7 (p.Pro29Leu) causes an autosomal recessive progeroid syndrome in a human patient. Proteomic comparison of mitochondria from patient-derived fibroblasts vs. controls revealed increased abundance of oxidative phosphorylation proteins and reduced abundance of phospholipid metabolism proteins, along with elevated basal and maximal oxygen consumption rates, consistent with altered mitochondrial protein import due to biallelic loss-of-function TOMM7. |
Exome sequencing, mitochondrial proteomics (quantitative MS), oxygen consumption rate measurement in patient-derived fibroblasts |
The Journal of clinical investigation |
Medium |
36282599
|
| 2022 |
A homozygous hypomorphic variant in TOMM7 (p.Trp25Arg) causes syndromic short stature with mitochondrial dysfunction. Mouse models homozygous for this variant show a milder phenotype than complete Tomm7 deletion mice. Tomm7 deficiency causes an uncoupling between oxidation and ATP synthesis without impairing the ETC or tricarboxylic acid cycle function, as evidenced by increased oxygen consumption with normal responses to ETC inhibitors. |
Mouse knock-in and knockout models, oxygen consumption assays, ETC inhibitor assays, patient variant analysis |
HGG advances |
Medium |
36299998
|
| 2025 |
TOMM7 regulates PINK1/Parkin-mediated mitophagy in kidney tubular cells by modulating the intracellular redistribution of phospholipase PLA2G6 between the nucleus and mitochondria. Tomm7 overexpression in db/db mice restored PINK1/Parkin-mediated mitophagy and alleviated kidney injury. ZBTB12 was identified as a transcriptional repressor of TOMM7. |
Tomm7 overexpression in db/db mice, HK-2 cell overexpression/knockdown, mitophagy flux assays, subcellular fractionation of PLA2G6, ChIP/transcription factor binding assays |
Kidney international |
Medium |
41276015
|
| 2025 |
CRISPR-Cas9 knockout of TOM7 in iPSC-derived dopaminergic neurons decreased ubiquitin pSer65 upregulation during mitophagy activation (induced by exogenous stimuli), confirming TOM7's role in the PINK1-PARKIN mitophagy pathway in a human neuronal model. |
High-throughput arrayed CRISPR-Cas9 KO screen in iPSC-derived dopaminergic neurons, high-content immunofluorescence imaging, machine learning analysis |
bioRxivpreprint |
Medium |
bio_10.1101_2025.06.10.658840
|