Affinage

TOMM20

Mitochondrial import receptor subunit TOM20 homolog · UniProt Q15388

Length
145 aa
Mass
16.3 kDa
Annotated
2026-04-28
92 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOMM20 is the principal presequence receptor of the translocase of the outer mitochondrial membrane (TOM) complex, mediating the initial recognition and import of nuclear-encoded mitochondrial proteins. Its cytosolic domain forms an all-alpha-helical fold with a hydrophobic groove that binds the amphipathic helical face of mitochondrial targeting sequences through a dynamic multi-pose equilibrium, while cooperating with Tom22 to hand off preproteins to the Tom40 translocation pore (PMID:10721992, PMID:17948058, PMID:37579144). Tom20 dynamically associates with and dissociates from the TOM core complex in response to substrate load, functions as a gatekeeper controlling preprotein entry into the pore, and serves as a docking platform for regulatory factors including PINK1 (forming a PINK1–TOM–TIM23 supercomplex for mitophagy), E3 ubiquitin ligases (Fbxo7, HUWE1, FEM1B-CRL2), and the chaperone cofactor AIP (PMID:34347503, PMID:38416681, PMID:14557246, PMID:40263465). Pathologically modified alpha-synuclein binds Tom20 with high affinity, disrupting the Tom20–Tom22 interaction and impairing mitochondrial protein import — a mechanism directly observed in Parkinson's disease brain tissue that is rescued by Tom20 overexpression in vivo (PMID:27280685, PMID:33293540).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 High

    Establishing the existence of a dedicated import receptor: the discovery that MOM19 antibodies inhibit high-affinity binding and import of precursor proteins across multiple mitochondrial subcompartments identified the first mitochondrial outer membrane import receptor.

    Evidence Immunoinhibition with monospecific IgG/Fab fragments and import assays in isolated Neurospora mitochondria

    PMID:2557158

    Open questions at the time
    • Substrate specificity not yet defined
    • Mammalian ortholog not yet identified
  2. 1994 High

    Defining substrate specificity: deletion of Tom20 in yeast selectively impaired import of cleavable presequence-bearing preproteins while leaving carrier protein import largely intact, establishing Tom20 as the primary presequence receptor distinct from Tom70.

    Evidence Gene disruption in S. cerevisiae combined with in vitro import assays using defined substrates; corroborated by Neurospora depletion showing severe growth and import defects

    PMID:8120088 PMID:8132642

    Open questions at the time
    • Molecular basis of presequence recognition unknown
    • Structural information absent
  3. 1995 High

    Demonstrating conservation and receptor cooperation: human TOMM20 complemented yeast Δmas20 respiratory defects, proving functional conservation, while biochemical studies showed Tom20 and Tom22 form a cooperative receptor complex for presequence recognition.

    Evidence Cross-species complementation in yeast; cross-linking and binding assays with purified outer membrane vesicles

    PMID:7556061 PMID:7589431

    Open questions at the time
    • Structural basis of Tom20–Tom22 cooperation not resolved
    • Human Tom20 structure not determined
  4. 2000 High

    Revealing the structural mechanism of presequence recognition: the NMR structure of the rat Tom20 cytosolic domain bound to a presequence peptide showed an all-alpha-helical fold with a hydrophobic groove that contacts the hydrophobic face of the amphipathic presequence helix, establishing that binding is primarily hydrophobic rather than electrostatic.

    Evidence NMR structure determination of Tom20–presequence complex

    PMID:10721992

    Open questions at the time
    • Only one presequence co-structure; diversity of binding modes not explored
    • Full-length Tom20 in membrane context not visualized
  5. 2007 High

    Understanding dynamic multi-pose recognition and membrane assembly: crystallography and NMR dynamics revealed that presequences adopt multiple binding poses in the Tom20 groove, while genetic and biochemical studies showed that Mim1 catalyzes Tom20 integration into the TOM complex via its transmembrane segment.

    Evidence X-ray crystallography of disulfide-tethered complex plus NMR relaxation; Mim1 deletion and TM mutagenesis in yeast

    PMID:17948058 PMID:18177669 PMID:18187149

    Open questions at the time
    • Full TOM holo complex structure not available
    • Tom20 dynamics in live cells not measured
  6. 2011 High

    Identifying Tom20 as a dynamic nanoscale-clustered receptor that interfaces with Tom70: super-resolution imaging revealed membrane potential–dependent clustering of Tom20, while biochemistry showed Tom20's C-terminal DDVE motif competes with chaperones for Tom70 TPR binding, integrating the two import receptor pathways.

    Evidence STED microscopy in >1000 cells; cross-linking, co-precipitation, NMR titrations, and SPR with purified proteins

    PMID:21771790 PMID:21799113

    Open questions at the time
    • Functional consequence of clustering not directly tested
    • In vivo significance of Tom20–Tom70 competition not established
  7. 2016 High

    Linking Tom20 to Parkinson's disease pathogenesis: posttranslationally modified alpha-synuclein was shown to bind Tom20 with high affinity, blocking the Tom20–Tom22 interaction and impairing mitochondrial protein import — a mechanism validated in human PD brain tissue.

    Evidence Co-immunoprecipitation, proximity ligation assay, in vitro import assays, and postmortem PD brain analysis

    PMID:27280685

    Open questions at the time
    • Whether therapeutic restoration of Tom20 function reverses established neurodegeneration unknown
    • Specific residues on Tom20 bound by alpha-synuclein not mapped
  8. 2019 High

    Establishing Tom20 as the PINK1 docking site for mitophagy signaling: PINK1 was shown to directly bind the Tom20 cytosolic domain, and disruption of this interaction prevented PINK1 complex formation and Parkin-mediated mitophagy.

    Evidence Co-immunoprecipitation and in vitro binding assays; drug (celastrol) disruption of PINK1–Tom20 interaction

    PMID:30885942

    Open questions at the time
    • Structural basis of PINK1–Tom20 interface not resolved at atomic level
  9. 2020 High

    Demonstrating sufficiency of Tom20 overexpression to rescue alpha-synuclein neurotoxicity: AAV2-mediated Tom20 overexpression in rat substantia nigra prevented dopaminergic neurodegeneration by restoring import of nuclear-encoded mitochondrial proteins.

    Evidence In vivo AAV2 co-expression in adult rat brain with stereological neuron counting and Western blot of imported proteins

    PMID:33293540

    Open questions at the time
    • Not tested in chronic progressive PD models
    • Downstream import substrates most critical for neuroprotection not identified
  10. 2022 High

    Resolving the architecture of Tom20 within the human TOM complex: cryo-EM structures at 2.5–6 Å revealed that Tom20 and Tom22 share a three-helix bundle cytosolic fold, with Tom20 positioned centrally in the holo complex stabilized by interactions with Tom22, Tom40, and Tom6.

    Evidence Cryo-EM of human TOM core and holo complex; structure-guided mutagenesis and presequence binding assays

    PMID:35733257 PMID:39071881

    Open questions at the time
    • Substrate-engaged human TOM structure not yet captured
    • Conformational dynamics between gatekeeper states not resolved at high resolution in human complex
  11. 2023 High

    Capturing Tom20 as a conformational gatekeeper: cryo-EM of the Neurospora TOM holo complex with a trapped preprotein showed Tom20 in two conformations, acting as a dynamic gatekeeper that guides substrates into Tom40 pores.

    Evidence Single-particle cryo-EM of TOM holo complex at 6–7 Å and preprotein-bound state at 4 Å

    PMID:37579144

    Open questions at the time
    • Transition kinetics between gatekeeper conformations not measured
    • Human preprotein-bound TOM structure not available
  12. 2024 High

    Expanding Tom20's role as a signaling and quality-control platform: PINK1 was shown to tether TOM and TIM23 into a supercomplex via its Tom20 interaction, while FEM1B-CRL2 and HUWE1 E3 ligases dock at Tom20 to ubiquitinate outer membrane substrates, and PCBP2–Tom20–SFXN3 was implicated in mitochondrial iron entry.

    Evidence Reciprocal co-IP in dopamine neurons and organoids with mutagenesis (PINK1–TOM–TIM23); proteomic, structural, and genetic approaches (FEM1B); in vitro ubiquitination and functional assays (HUWE1); GST pulldown and PLA (PCBP2–SFXN3)

    PMID:38184713 PMID:38416681 PMID:38599240 PMID:40263465

    Open questions at the time
    • Structural basis of E3 ligase docking on Tom20 not determined
    • Iron transport role requires direct flux measurements
    • Relative contributions of HUWE1 vs Fbxo7 vs PARKIN to Tom20 ubiquitination in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic-resolution structure of a substrate-engaged human TOM holo complex capturing the full translocation cycle — from presequence recognition by Tom20 through handoff to Tom22 and threading into Tom40 — has not been obtained, and the regulatory logic governing Tom20 post-translational modification by multiple E3 ligases remains unintegrated.
  • No high-resolution structure of human TOM with translocating preprotein
  • Hierarchy and context-dependence of Tom20 ubiquitination by Fbxo7/HUWE1/PARKIN not resolved
  • Whether Tom20's non-canonical interactions (AR stabilization, iron transport) reflect physiological functions or overexpression artifacts is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 6 GO:0005198 structural molecule activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005739 mitochondrion 7 GO:0005886 plasma membrane 2
Pathway
R-HSA-9609507 Protein localization 7 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 3 R-HSA-5357801 Programmed Cell Death 2
Partners
AIPFBXO7FEM1BPINK1SNCATOMM22TOMM40TOMM70
Complex memberships
PINK1-TOM-TIM23 supercomplexTOM complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 MOM19 (the Neurospora/yeast ortholog of TOMM20) was identified as a mitochondrial outer membrane protein that functions as an import receptor; antibodies against MOM19 inhibit high-affinity binding and import of precursor proteins destined for multiple mitochondrial subcompartments. Immunoinhibition with monospecific IgG/Fab fragments; import assays with isolated mitochondria Cell High 2557158
1991 MOM19 (TOMM20 ortholog) is anchored in the outer membrane via an NH2-terminal hydrophobic sequence, with the remainder forming a cytosolic hydrophilic domain; its own targeting to mitochondria is independent of protease-accessible surface receptors and occurs via direct assembly with the general insertion pore (GIP). Gene cloning, sequence analysis, in vitro import assays Science High 1661031
1993 Yeast MOM19 (TOMM20 ortholog) is exposed on the outer membrane surface, present in the mitochondrial receptor complex, and its antibody inhibition blocks preprotein import; MOM19 can function independently of MOM72 (Tom70). Antibody inhibition of import; genetic deletion of MOM72; isolated mitochondria import assays FEBS letters High 8392001
1994 Deletion of MOM19 in yeast strongly inhibits import of cleavable preproteins but only slightly inhibits import of non-cleavable ADP/ATP carrier and phosphate carrier, establishing that MOM19 plays a major role specifically for cleavable presequence-bearing preproteins. Gene disruption (delta MOM19) in S. cerevisiae; in vitro import assays with isolated mitochondria The Journal of biological chemistry High 8132642
1994 Depletion of MOM19 in Neurospora crassa causes severe growth defect, loss of cristae membranes, and 6–30-fold reduction in protein import from all subcompartments; loss of MOM19 also reduces MOM22 levels, revealing a functional interdependence between the two receptors. Sheltered RIP mutagenesis; protein import assays; electron microscopy of mutant mitochondria The Journal of cell biology High 8120088
1995 MOM22 and MOM19 form a complex that functions as the presequence receptor; both directly bind preproteins at the mitochondrial surface in a salt-sensitive (electrostatic) manner, with MOM22 recognizing presequences via its acidic cytosolic domain. Cross-linking; binding assays with purified outer membrane vesicles; inactivation of MOM22 or MOM19 The EMBO journal High 7556061
1995 The human TOMM20 homolog (huMas20p) is inserted into the outer mitochondrial membrane in Nin-Ccyto orientation, and antibodies against its soluble domain inhibit import of diverse precursor proteins; expression of huMAS20 complements the respiratory defect of delta mas20 yeast. In vitro import into isolated rat heart mitochondria; antibody inhibition; complementation of yeast delta mas20 FEBS letters High 7589431
1995 Human TOMM20 (16 kDa) specifically associates with the outer membrane receptor complex of yeast mitochondria when synthesized in vitro, demonstrating conserved function across species. In vitro import and co-fractionation with yeast mitochondria FEBS letters Medium 7498524
1997 Purified cytosolic domains of Tom20, Tom22, and Tom70 each independently bind mitochondrial preproteins but with different specificity: Tom20 binds both presequence-carrying and internal-signal preproteins (binding enhanced by salt); Tom22 selectively recognizes presequence-carrying preproteins (salt-sensitive); Tom70 prefers internal targeting information. Purified recombinant cytosolic domains; preprotein binding assays; presequence peptide competition The Journal of biological chemistry High 9252394
1997 The linker segment (charged amino acids-rich region between the membrane anchor and the TPR motif) of rat Tom20 is essential for function; the TPR motif and C-terminal acidic amino acids are dispensable for complementation of delta tom20 yeast. Expression of Tom20 truncation mutants in delta tom20 yeast; in vitro protein import assays The Journal of biological chemistry High 9218491
1997 Human TOMM20 overexpression in COS-7 cells stimulates mitochondrial import of pOTC-GFP (presequence-bearing substrate), while a truncation lacking the membrane anchor (DeltahTom20) does not; overexpression also causes perinuclear aggregation of mitochondria. Transfection; pulse-chase import assay; GFP live imaging; cell fractionation The Journal of biological chemistry Medium 9079673
1998 The N-terminal region of the human TOMM20 cytosolic domain (aa50–90) binds matrix targeting signals (presequences) preferably in their alpha-helical conformation with a Kd of ~0.6 µM; the C-terminal region (aa90–145) recognizes internal targeting signals of uncoupling protein and porin. GST fusion protein binding assays; secondary structure induction by detergent; proteolysis protection Biochemistry Medium 9748309
1998 Human TOMM20 (hTom20) region aa30–60 is involved in membrane binding and recognition of cleavable matrix targeting signals; the glutamine-rich segment (residues 106–125) is essential for binding and import stimulation of pOTC-GFP in vivo and for inhibition of in vitro import. Truncation mutants; overexpression in COS-7 cells; in vitro import assays; preprotein binding assays The Journal of biological chemistry High 9756929
1999 Tom20 catalyzes direct insertion of VDAC (a beta-barrel outer membrane protein) into lipid bilayers independently of the Tom40 translocation pore; synthetic liposomes bearing only the cytosolic domain of human Tom20 are sufficient to insert VDAC and produce a functional transmembrane ATP-transporting channel. Reconstitution in synthetic liposomes; Tom40 pore-plugging experiment; temperature-sensitive Tom40 mutant mitochondria; ATP transport assay The Journal of cell biology High 10352015
1999 Tom20, Tom22, and Tom70 each bind different linear peptide segments of both presequence-containing and internal-signal preproteins; Tom20 preferentially binds presequence segments and multiple regions of the phosphate carrier, while Tom70 and Tom20 both bind multiple segments of the phosphate carrier. Cellulose-bound peptide scans; binding of purified cytosolic receptor domains The Journal of biological chemistry High 10347216
2000 NMR structure of rat Tom20 cytosolic domain in complex with a presequence peptide (from rat aldehyde dehydrogenase) reveals an all-alpha-helical structure with a hydrophobic groove; the presequence forms an amphiphilic helix with hydrophobic leucines interacting with the Tom20 hydrophobic patch — binding is mediated mainly by hydrophobic rather than ionic interactions. NMR structure determination of Tom20–presequence complex Cell High 10721992
2000 The mitochondria-targeting signal of rat Tom20 requires moderate TMD hydrophobicity and a net positive charge within five residues of the COOH-terminal flanking region; high TMD hydrophobicity or lack of positive charge redirects the protein to ER-Golgi. SRP recognizes the TMD but with reduced affinity, and the positive charge inhibits SRP-induced translation arrest. GFP reporter fusions with systematic deletions/mutations; fluorescence microscopy; cell fractionation; SRP photo-cross-linking; in vitro import assays The Journal of cell biology High 11038175
2001 NMR chemical shift perturbation mapping across five different presequence peptides reveals that the Tom20-binding segments occupy different positions (near N terminus or at C terminus) within presequences, and spin-label experiments show these different positions do not reflect different orientations of the peptide in the binding groove. NMR chemical shift perturbation; spin-label experiments with 15N-labeled presequences Journal of molecular biology High 11237589
2003 AIP (arylhydrocarbon receptor-interacting protein) binds Tom20 via tetratricopeptide repeats interacting with the extreme C-terminal acidic segment of Tom20, and also binds preproteins directly; formation of a ternary Tom20–AIP–preprotein complex facilitates import-competent state of preproteins (chaperone-like activity). Yeast two-hybrid screen; in vitro import assays; RNAi knockdown; co-immunoprecipitation; aggregation suppression assay The Journal of cell biology High 14557246
2003 The cytosolic domain of Tom20 has chaperone-like activity, preventing substrate proteins (citrate synthase) from aggregating; this activity is inhibited by presequence peptides, indicating the presequence-binding site and chaperone active site overlap. Tom22 cytosolic domain has similar activity; Tom70 does not. Aggregation suppression assay; presequence peptide competition; in vitro binding The Journal of biological chemistry Medium 14699115
2007 Tom20 and Tom22 are involved in the same step or sequential steps of targeting signal recognition for import of diverse substrates; selective in vitro deletion of receptor domains shows their effects on different import pathways are nearly identical. In vitro protease-cleavage of receptor domains via introduced tobacco etch virus protease sites; import assays with multiple substrates The Journal of biological chemistry High 18063580
2007 Tom20 recognizes mitochondrial presequences through a dynamic equilibrium among multiple bound states (A-, M-, and Y-poses); crystallization required tethering the presequence via disulfide bond, and NMR 15N relaxation revealed sub-millisecond timescale motions at the Tom20–presequence interface. X-ray crystallography of disulfide-tethered Tom20–presequence complex; NMR 15N relaxation analysis The EMBO journal High 17948058
2007 The transmembrane segment of Tom20 contains residues essential for docking into the TOM complex, and this docking reaction is catalyzed by the assembly factor Mim1/Tom13; mutations in the TM segment or deletion of Mim1 prevent Tom20 from functioning as an import receptor. Mutagenesis of Tom20 TM segment; Mim1 deletion; in vitro import assays in yeast Journal of molecular biology High 18187149
2007 Mim1 forms homo-oligomers via GXXXG motifs in its transmembrane segment, and this oligomerization is required for Mim1's function in promoting integration of Tom20 into the outer mitochondrial membrane; mutated GXXXG motifs abolish both oligomerization and function. Co-immunoprecipitation; mutagenesis of GXXXG motifs; import assays in yeast Journal of molecular biology High 18177669
2010 Tom20 deletion in yeast reduces mRNA association of most mitochondrial-protein-encoding mRNAs with mitochondria in a translation-dependent and mitochondrial targeting signal-dependent manner; a tom20Δ puf3Δ double knockout shows additive mRNA mislocalization, placing Tom20 in a co-translational import pathway alongside Puf3p. DNA microarray of mRNAs from mitochondrial fractions of delta tom20 yeast; genetic epistasis (double knockout); ribosome/translation dependence analysis Molecular and cellular biology High 19858288
2010 Tom20 has a dual role in mitochondrial protein import: the N-terminal Tom20-binding element of a presequence is essential for targeting, while a C-terminal element increases import efficiency by tethering the presequence to the TOM40 complex prior to translocation across the inner membrane. NMR spectroscopy of presequence–Tom20 interaction; in vitro import assays; cross-linking experiments Proceedings of the National Academy of Sciences of the United States of America High 21173275
2011 Tom20 is located in clusters in the mitochondrial outer membrane whose nanoscale distribution correlates with mitochondrial membrane potential; Tom20 and Tom22 clusters follow an inner-cellular gradient from perinuclear to peripheral mitochondria, adjusting to growth conditions. Super-resolution STED microscopy of >1000 cells; quantitative cluster analysis Proceedings of the National Academy of Sciences of the United States of America Medium 21799113
2011 Human Tom20 interacts with the TPR clamp domain of Tom70 via a conserved C-terminal DDVE motif; this interaction competes with Hsc70/Hsp90 for Tom70 binding, suggesting Tom20 facilitates preprotein release from chaperones for Tom70-mediated import. Cross-linking of endogenous proteins; co-precipitation; NMR titrations; surface plasmon resonance; mutagenesis of DDVE motif The Journal of biological chemistry High 21771790
2016 Posttranslationally modified (nitrated, S129 phosphorylated) alpha-synuclein binds with high affinity to the TOM20 presequence receptor, preventing TOM20–TOM22 interaction and impairing mitochondrial protein import, leading to deficient respiration, ROS production, and loss of membrane potential; this aberrant alpha-synuclein–TOM20 interaction was confirmed in postmortem Parkinson's disease brain tissue. Co-immunoprecipitation; in vitro import assays; proximity ligation assay; overexpression and knockdown in cell lines and in vivo PD models; postmortem PD brain tissue analysis Science translational medicine High 27280685
2016 Fbxo7 (SCF^PARK15 ubiquitin ligase) ubiquitinates TOMM20 both in vitro and in vivo; Fbxo7 levels correlate with TOMM20 stability (stabilizing effect), and ubiquitinated TOMM20 promotes mitophagy. Protein array high-throughput substrate screen; in vitro ubiquitination assay; ubiquitin chain restriction analysis; co-immunoprecipitation The Biochemical journal Medium 27503909
2018 Iron-activated ROS causes oxidation and oligomerization of Tom20 in melanoma cells; oxidized Tom20 recruits Bax to mitochondria, facilitating cytochrome c release, caspase-3 activation, and GSDME cleavage to trigger pyroptosis — establishing a Tom20–Bax–caspase–GSDME pyroptotic pathway. Western blot; siRNA knockdown of Tom20; co-immunoprecipitation of Tom20 and Bax; immunofluorescence; xenograft tumor models Cell research High 30287942
2019 PINK1 directly and strongly associates with TOM20 (a component of the TOM machinery); celastrol disrupts PINK1–TOM20 binding both in vitro and in vivo, prevents PINK1 complex formation upon mitochondrial depolarization, and blocks Parkin recruitment and mitophagy. Co-immunoprecipitation; native gel analysis; in vitro binding assays; high-throughput drug screen; immunofluorescence The Journal of biological chemistry High 30885942
2020 Overexpression of TOM20 in rat substantia nigra via AAV2 prevents alpha-synuclein-induced dopaminergic neurodegeneration by rescuing expression of nuclear-encoded mitochondrial electron transport chain proteins and GRP75/mtHSP70, demonstrating that preserved mitochondrial import is sufficient to block alpha-synuclein toxicity. AAV2 co-expression in adult rat brain; stereological counting of dopaminergic neurons; Western blot for imported mitochondrial proteins NPJ Parkinson's disease High 33293540
2021 TOM20 controls Bcl2 localization at mitochondria upon apoptosis induction; Bcl2 is translocated from ER to MAM and then mitochondria in a TOM20-dependent manner, and the Bcl2–TOM20 interaction is proapoptotic. This was validated in a yeast ERMES-disruption model. Subcellular fractionation; co-immunoprecipitation; yeast ERMES disruption complementation; overexpression of TOM20–Bcl2 interaction domain Cell death & disease Medium 33589622
2021 Tom20 is dynamically associated with the TOM core complex in human mitochondria — single-particle tracking shows Tom20 has higher lateral mobility than the TOM core; ligation of Tom20 to Tom7 decreases Tom20 diffusion, and high substrate loading reduces Tom20 mobility, suggesting Tom20 associates with the active import pore when substrate is available. Single-particle tracking in live human cells; post-translational protein trans-splicing (Gp41-1 system); FRAP-like mobility analysis Molecular biology of the cell High 34347503
2022 Cryo-EM structure of the human TOM complex at 2.53 Å (core) and 3.74 Å (holo with Tom20 and Tom22 cytosolic domains) reveals that Tom20 and Tom22 share a similar three-helix bundle cytosolic domain; structure-guided biochemical analysis shows the Tom22 cytosolic domain (helix H1) is primarily responsible for presequence binding. Cryo-EM structure determination; structure-guided mutagenesis; biochemical presequence binding assays Proceedings of the National Academy of Sciences of the United States of America High 35733257
2023 Cryo-EM structure of the Neurospora crassa TOM holo complex at 6–7 Å resolution reveals Tom20 in two conformations (gatekeeper dynamics), with a transmembrane helix and cytoplasmic receptor domain; Tom20 acts as a dynamic gatekeeper guiding preproteins into the TOM40 pores. Single-particle cryo-EM of TOM core (3.3 Å) and holo complex (6–7 Å); bound preprotein structure at 4 Å Proceedings of the National Academy of Sciences of the United States of America High 37579144
2024 PINK1 directly interacts with the cytosolic domain of Tom20 via its N-terminal–C-terminal extension module; upon mitochondrial stress, PINK1 tethers the TOM and TIM23 complexes forming a PINK1–TOM–TIM23 supercomplex; disruption of this interaction (by designer or PD-associated PINK1 mutations) inhibits downstream mitophagy. Co-immunoprecipitation; human cell lines, dopamine neurons, and midbrain organoids; mutagenesis of PINK1 interaction interface; mitophagy assays Proceedings of the National Academy of Sciences of the United States of America High 38416681
2024 HUWE1 E3 ligase directly ubiquitinates TOMM20 and also regulates TOMM20 degradation via the PARKIN-mediated pathway; HUWE1 overexpression reduces mitochondrial function (ATP, membrane potential) and increases ROS/apoptosis, sensitizing CRC cells to oxaliplatin. Co-immunoprecipitation; in vitro ubiquitination assay; HUWE1 overexpression/knockdown; mitochondrial function assays Oncogene Medium 38184713
2024 Cryo-EM structure of the human TOM holo complex (including intact Tom20) at ~6 Å resolution, stabilized by chemical cross-linking, shows one Tom20 subunit at the center of the complex, stabilized by extensive interactions with Tom22, Tom40, and Tom6. Chemical cross-linking to stabilize Tom20; cryo-EM structure determination PNAS nexus High 39071881
2024 TOM20 directly interacts with SFXN3 (sideroflexin-3, an inner membrane protein), and PCBP2 (cytosolic Fe(II) chaperone) associates proximally with TOM20; this PCBP2–TOM20–SFXN3 axis represents a pathway for iron entry into mitochondria from the cytosol. GST pulldown; LC-MS identification; co-immunoprecipitation; proximity ligation assay; STED microscopy; SFXN3/MFRN1 knockout mouse embryonic fibroblasts Free radical research Medium 38599240
2025 FEM1B (substrate receptor of CRL2 E3 ligase) directly associates with TOM20 at the mitochondrial outer membrane and uses this interaction to degrade PLD6 (a regulator of mitochondrial dynamics); disruption of the FEM1B–TOM20 interaction impairs PLD6 degradation and induces mitochondrial morphology defects. Proteomic analysis; structural and biochemical approaches; co-immunoprecipitation; FEM1B ablation; mitochondrial morphology assays Nature chemical biology High 40263465
2025 TOMM20 physically interacts with androgen receptor (AR) and stabilizes AR protein; TOMM20 knockdown promotes AR degradation via SKP2-mediated ubiquitin-proteasome pathway, independently of HSP90/HSP70, and reduces AR transcriptional activity. Co-immunoprecipitation; GST pulldown; RNA-seq; ChIP; siRNA knockdown; ubiquitination assays Oncogene Medium 40044984

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis. Cell research 521 30287942
2016 α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease. Science translational medicine 487 27280685
2000 Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 456 10721992
1989 MOM19, an import receptor for mitochondrial precursor proteins. Cell 294 2557158
1997 Differential recognition of preproteins by the purified cytosolic domains of the mitochondrial import receptors Tom20, Tom22, and Tom70. The Journal of biological chemistry 230 9252394
1999 Distribution of binding sequences for the mitochondrial import receptors Tom20, Tom22, and Tom70 in a presequence-carrying preprotein and a non-cleavable preprotein. The Journal of biological chemistry 195 10347216
2000 Characterization of the signal that directs Tom20 to the mitochondrial outer membrane. The Journal of cell biology 179 11038175
2001 Purification and characterization of the preprotein translocase of the outer mitochondrial membrane from Arabidopsis. Identification of multiple forms of TOM20. Plant physiology 152 11161051
2010 Tom20 mediates localization of mRNAs to mitochondria in a translation-dependent manner. Molecular and cellular biology 143 19858288
2007 Tom20 and Tom22 share the common signal recognition pathway in mitochondrial protein import. The Journal of biological chemistry 131 18063580
2011 Nanoscale distribution of mitochondrial import receptor Tom20 is adjusted to cellular conditions and exhibits an inner-cellular gradient. Proceedings of the National Academy of Sciences of the United States of America 129 21799113
2007 Tom20 recognizes mitochondrial presequences through dynamic equilibrium among multiple bound states. The EMBO journal 126 17948058
1995 MOM22 is a receptor for mitochondrial targeting sequences and cooperates with MOM19. The EMBO journal 120 7556061
1994 Deletion of the receptor MOM19 strongly impairs import of cleavable preproteins into Saccharomyces cerevisiae mitochondria. The Journal of biological chemistry 106 8132642
1991 Targeting of the master receptor MOM19 to mitochondria. Science (New York, N.Y.) 103 1661031
1994 A crucial role of the mitochondrial protein import receptor MOM19 for the biogenesis of mitochondria. The Journal of cell biology 98 8120088
2010 Dual role of the receptor Tom20 in specificity and efficiency of protein import into mitochondria. Proceedings of the National Academy of Sciences of the United States of America 92 21173275
2007 The transmembrane segment of Tom20 is recognized by Mim1 for docking to the mitochondrial TOM complex. Journal of molecular biology 92 18187149
2007 Mim1 functions in an oligomeric form to facilitate the integration of Tom20 into the mitochondrial outer membrane. Journal of molecular biology 90 18177669
1995 Identification of the human mitochondrial protein import receptor, huMas20p. Complementation of delta mas20 in yeast. FEBS letters 86 7589431
2003 AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins. The Journal of cell biology 78 14557246
2001 NMR identification of the Tom20 binding segment in mitochondrial presequences. Journal of molecular biology 74 11237589
1997 Visualization of mitochondrial protein import in cultured mammalian cells with green fluorescent protein and effects of overexpression of the human import receptor Tom20. The Journal of biological chemistry 69 9079673
1995 A human homolog of the mitochondrial protein import receptor Mom19 can assemble with the yeast mitochondrial receptor complex. FEBS letters 56 7498524
1999 Direct membrane insertion of voltage-dependent anion-selective channel protein catalyzed by mitochondrial Tom20. The Journal of cell biology 55 10352015
2024 Tom20 gates PINK1 activity and mediates its tethering of the TOM and TIM23 translocases upon mitochondrial stress. Proceedings of the National Academy of Sciences of the United States of America 54 38416681
2022 Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors. Proceedings of the National Academy of Sciences of the United States of America 52 35733257
1997 Analysis of the functional domain of the rat liver mitochondrial import receptor Tom20. The Journal of biological chemistry 51 9218491
1993 The protein import receptor MOM19 of yeast mitochondria. FEBS letters 51 8392001
2021 TOM20-mediated transfer of Bcl2 from ER to MAM and mitochondria upon induction of apoptosis. Cell death & disease 49 33589622
2010 Recognition of mitochondrial targeting sequences by the import receptors Tom20 and Tom22. Journal of molecular biology 48 21087612
2011 Interaction between the human mitochondrial import receptors Tom20 and Tom70 in vitro suggests a chaperone displacement mechanism. The Journal of biological chemistry 47 21771790
2005 Patterns that define the four domains conserved in known and novel isoforms of the protein import receptor Tom20. Journal of molecular biology 45 15733919
1998 Functional and structural properties of the mitochondrial outer membrane receptor Tom20. Biochemistry 45 9748309
1998 Functional analysis of human mitochondrial receptor Tom20 for protein import into mitochondria. The Journal of biological chemistry 45 9756929
2019 TOMM20 as a potential therapeutic target of colorectal cancer. BMB reports 44 31818360
2003 Peptide library approach with a disulfide tether to refine the Tom20 recognition motif in mitochondrial presequences. Journal of molecular biology 44 12691756
2000 Tom20-mediated mitochondrial protein import in muscle cells during differentiation. American journal of physiology. Cell physiology 43 11029287
2003 Mitochondrial import receptors Tom20 and Tom22 have chaperone-like activity. The Journal of biological chemistry 41 14699115
2016 Gsk3β and Tomm20 are substrates of the SCFFbxo7/PARK15 ubiquitin ligase associated with Parkinson's disease. The Biochemical journal 40 27503909
2023 Iron induces B cell pyroptosis through Tom20-Bax-caspase-gasdermin E signaling to promote inflammation post-spinal cord injury. Journal of neuroinflammation 32 37480037
1997 Human mitochondrial import receptor, Tom20p. Use of glutathione to reveal specific interactions between Tom20-glutathione S-transferase and mitochondrial precursor proteins. FEBS letters 32 9119086
2023 Neobavaisoflavone induces pyroptosis of liver cancer cells via Tom20 sensing the activated ROS signal. Phytomedicine : international journal of phytotherapy and phytopharmacology 30 37196512
2021 The receptor subunit Tom20 is dynamically associated with the TOM complex in mitochondria of human cells. Molecular biology of the cell 30 34347503
2006 Prevention of the ischemia-induced decrease in mitochondrial Tom20 content by ischemic preconditioning. Journal of molecular and cellular cardiology 29 16828795
1997 Participation of the import receptor Tom20 in protein import into mammalian mitochondria: analyses in vitro and in cultured cells. FEBS letters 28 9091323
1994 Inactivation of the Neurospora crassa gene encoding the mitochondrial protein import receptor MOM19 by the technique of "sheltered RIP". Genetics 28 8138148
2020 Translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20) facilitates cancer aggressiveness and therapeutic resistance in chondrosarcoma. Biochimica et biophysica acta. Molecular basis of disease 27 32920118
2020 Protection from α-Synuclein induced dopaminergic neurodegeneration by overexpression of the mitochondrial import receptor TOM20. NPJ Parkinson's disease 27 33293540
2019 The plant triterpenoid celastrol blocks PINK1-dependent mitophagy by disrupting PINK1's association with the mitochondrial protein TOM20. The Journal of biological chemistry 25 30885942
2010 Glycine-rich loop of mitochondrial processing peptidase alpha-subunit is responsible for substrate recognition by a mechanism analogous to mitochondrial receptor Tom20. Journal of molecular biology 24 20053354
1998 Characterization of the N-terminal targeting signal binding domain of the mitochondrial outer membrane receptor, Tom20. Biochemistry 23 9748310
2012 Immunocytochemical localization of the translocase of the outer mitochondrial membrane (Tom20) in the human cochlea. Anatomical record (Hoboken, N.J. : 2007) 22 23165776
2023 Two conformations of the Tom20 preprotein receptor in the TOM holo complex. Proceedings of the National Academy of Sciences of the United States of America 21 37579144
2009 Mitochondrial targeting of cytochrome P450 proteins containing NH2-terminal chimeric signals involves an unusual TOM20/TOM22 bypass mechanism. The Journal of biological chemistry 20 19401463
2002 Tom34 unlike Tom20 does not interact with the leader sequences of mitochondrial precursor proteins. Archives of biochemistry and biophysics 19 11913975
2011 Crystallographic snapshots of Tom20-mitochondrial presequence interactions with disulfide-stabilized peptides. Biochemistry 18 21591667
2010 The molecular recognition mechanism for superoxide dismutase presequence binding to the mitochondrial protein import receptor Tom20 from Oryza sativa involves an LRTLA motif. The journal of physical chemistry. B 18 20936826
1999 Gene structure of the human mitochondrial outer membrane receptor Tom20 and evolutionary study of its family of processed pseudogenes. Gene 17 10548729
2023 Hsp70-Bim interaction facilitates mitophagy by recruiting parkin and TOMM20 into a complex. Cellular & molecular biology letters 16 37237369
2023 AR antagonists develop drug resistance through TOMM20 autophagic degradation-promoted transformation to neuroendocrine prostate cancer. Journal of experimental & clinical cancer research : CR 14 37563661
2021 PRR34-AS1 sponges miR-498 to facilitate TOMM20 and ITGA6 mediated tumor progression in HCC. Experimental and molecular pathology 14 33609562
2005 Import of rat mitochondrial citrate carrier (CIC) at increasing salt concentrations promotes presequence binding to import receptor Tom20 and inhibits membrane translocation. Journal of cell science 13 16129883
1998 Interaction between mitochondrial precursor proteins and cytosolic soluble domains of mitochondrial import receptors, Tom20 and Tom70, measured by surface plasmon resonance. Biochemical and biophysical research communications 13 9918781
2022 Dual Effects of Korean Red Ginseng on Astrocytes and Neural Stem Cells in Traumatic Brain Injury: The HO-1-Tom20 Axis as a Putative Target for Mitochondrial Function. Cells 12 35269514
2024 Neobractatin induces pyroptosis of esophageal cancer cells by TOM20/BAX signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 10 38547615
2022 ATP13A2 modifies mitochondrial localization of overexpressed TOM20 to autolysosomal pathway. PloS one 10 36445873
2006 Binding of mitochondrial leader sequences to Tom20 assessed using a bacterial two-hybrid system shows that hydrophobic interactions are essential and that some mutated leaders that do not bind Tom20 can still be imported. Protein science : a publication of the Protein Society 10 17088320
2025 TOM20-driven E3 ligase recruitment regulates mitochondrial dynamics through PLD6. Nature chemical biology 9 40263465
2020 Dexamethasone upregulates mitochondrial Tom20, Tom70, and MnSOD through SGK1 in the kidney cells. Journal of physiology and biochemistry 9 33201408
2016 Methylation quantitative trait loci within the TOMM20 gene are associated with metabolic syndrome-related lipid alterations in severely obese subjects. Diabetology & metabolic syndrome 9 27478511
2013 Energetics of the presequence-binding poses in mitochondrial protein import through Tom20. The journal of physical chemistry. B 9 23432372
2005 Crystallization and preliminary X-ray analysis of mitochondrial presequence receptor Tom20 in complexes with a presequence from aldehyde dehydrogenase. Acta crystallographica. Section F, Structural biology and crystallization communications 9 16511083
2024 The E3 ligase HUWE1 increases the sensitivity of CRC to oxaliplatin through TOMM20 degradation. Oncogene 8 38184713
2024 Structure of the intact Tom20 receptor in the human translocase of the outer membrane complex. PNAS nexus 7 39071881
2023 Endogenous TOM20 Proximity Labeling: A Swiss-Knife for the Study of Mitochondrial Proteins in Human Cells. International journal of molecular sciences 5 37298552
2022 Angiotensin-(1-7) promotes mitochondrial translocation of human telomerase reverse transcriptase in HUVECs through the TOM20 complex. Archives of biochemistry and biophysics 5 35430213
2022 Both metaxin and Tom20 together with two mitochondria-specific motifs support mitochondrial targeting of dual-targeting AtSufE1. Journal of integrative plant biology 5 35713200
2008 An unusual TOM20/TOM22 bypass mechanism for the mitochondrial targeting of cytochrome P450 proteins containing N-terminal chimeric signals. The Journal of biological chemistry 5 18480056
2024 Association of poly(rC)-binding protein-2 with sideroflexin-3 through TOM20 as an iron entry pathway to mitochondria. Free radical research 4 38599240
2012 NMR investigations of the dual targeting peptide of Thr-tRNA synthetase and its interaction with the mitochondrial Tom20 receptor in Arabidopsis thaliana. The FEBS journal 4 22863398
1999 Identification of psi3Tom20, a novel processed pseudogene of the human Tom20 gene, and complete characterization of psi1Tom20 and psi2Tom20. Molecular & general genetics : MGG 4 10517315
2025 A mitochondrial outer membrane protein TOMM20 maintains protein stability of androgen receptor and regulates AR transcriptional activity in prostate cancer cells. Oncogene 3 40044984
2019 EAE-induced upregulation of mitochondrial MnSOD is associated with increases of mitochondrial SGK1 and Tom20 protein in the mouse kidney cortex. The journal of physiological sciences : JPS 3 31177508
1998 Identification of two processed psuedogenes of the human Tom20 gene. Molecular & general genetics : MGG 3 9613579
2026 Immunohistochemical Analysis of Tom20 in Choroid Plexus Epithelial Cells From Elderly Brains With Neurodegenerative Diseases. Neuropathology : official journal of the Japanese Society of Neuropathology 2 41565461
2025 TOMM20 as a driver of cancer aggressiveness via oxidative phosphorylation, maintenance of a reduced state, and resistance to apoptosis. Molecular oncology 2 39996379
2025 Using Metal-Organic Framework Nanoparticles for Targeted Codelivery of Bortezomib and Iron Ions to Mitochondrial TOM20 to Induce Ferroptosis for Colorectal Cancer Treatment. Molecular pharmaceutics 1 40671590
2025 Proximity Labeling Reveals RNA-Binding Proteins Associating with the Human Mitochondrial Import Receptor TOMM20. Journal of proteome research 1 41427806
2024 TMCO1 regulates energy metabolism and mitochondrial function of hepatocellular carcinoma cells through TOMM20, affecting the growth of subcutaneous graft tumors and infiltration of CAFs. Biochemistry and cell biology = Biochimie et biologie cellulaire 1 39566034
2022 Effects of targeting signal mutations in a mitochondrial presequence on the spatial distribution of the conformational ensemble in the binding site of Tom20. Protein science : a publication of the Protein Society 1 36173160
2025 GATA-1-driven TOMM20-mediated mitophagy regulates PDLSCs osteogenesis and enhances periodontal bone regeneration. Biochemical and biophysical research communications 0 41389613