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Showing TOMM20 — TOM20 is a alias.

TOMM20

Mitochondrial import receptor subunit TOM20 homolog · UniProt Q15388

Length
145 aa
Mass
16.3 kDa
Annotated
2026-06-10
91 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOMM20 is the principal cytosolic receptor of the mitochondrial outer-membrane TOM translocase, recognizing N-terminal presequences to direct cleavable preproteins into the matrix, inner membrane, and intermembrane space (PMID:2557158, PMID:8132642). It is anchored in the outer membrane by an N-terminal hydrophobic segment in an Nin-Ccyto orientation, leaving an all-α-helical cytosolic domain that captures presequences as amphiphilic helices within a hydrophobic groove (PMID:1661031, PMID:10721992); recognition is dynamic, sampling multiple bound orientations on a sub-millisecond timescale, with an N-terminal presequence element conferring targeting specificity and a C-terminal element raising import efficiency (PMID:17948058, PMID:21173275). Tom20 operates not in isolation but as a co-receptor system: it cooperates with Tom22 in sequential presequence recognition and with Tom70 in handling internal-signal carriers, displacing Hsp70/Hsp90 chaperones from Tom70 via its C-terminal DDVE motif (PMID:9252394, PMID:18063580, PMID:21771790). Its transmembrane segment is integrated into the membrane and docked into the TOM complex by the assembly factor Mim1, and within the assembled holo complex Tom20 is a dynamically associated, mobile gatekeeper stabilized by interactions with Tom22, Tom40, and Tom6 that gate preprotein entry into the Tom40 pore (PMID:18187149, PMID:34347503, PMID:37579144, PMID:39071881). Beyond canonical import, Tom20 can directly insert VDAC into lipid bilayers independently of the Tom40 pore (PMID:10352015), promotes translation-coupled localization of nuclear-encoded mitochondrial mRNAs to the mitochondrial surface (PMID:19858288), and serves as a docking platform for stress signaling: PINK1 tethers TOM to TIM23 through the Tom20 cytosolic domain to drive mitophagy (PMID:38416681), while ROS-induced oxidation of Tom20 recruits Bax to trigger caspase-3/GSDME pyroptosis (PMID:30287942). TOMM20 levels and function are controlled by ubiquitination through SCF-Fbxo7 and HUWE1 E3 ligases (PMID:27503909, PMID:38184713), and it acts as a platform recruiting FEM1B-CRL2 to degrade PLD6 and regulate mitochondrial morphology (PMID:40263465). In Parkinson's disease, modified α-synuclein binds TOM20 with high affinity, blocking the TOM20-TOM22 interaction and impairing protein import, respiration, and membrane potential (PMID:27280685).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 High

    Established that a 19 kDa outer-membrane protein acts as a surface import receptor, defining the existence of a presequence-recognition step before pore translocation.

    Evidence Antibody/Fab inhibition of in vitro import and immunoprecipitation

    PMID:2557158

    Open questions at the time
    • Did not define the membrane topology or the molecular basis of presequence binding
    • Did not distinguish direct binding from indirect receptor association
  2. 1991 High

    Defined the protein's architecture and biogenesis, showing it is N-terminally membrane-anchored with a cytosolic domain and inserts via the general insertion site independent of surface receptors.

    Evidence Gene cloning, sequence analysis, in vitro targeting and protease protection

    PMID:1661031

    Open questions at the time
    • Did not identify the assembly machinery responsible for membrane integration
    • Structure of the cytosolic domain unresolved
  3. 1994 High

    Genetic loss-of-function established TOMM20 as the primary receptor specifically for cleavable presequence preproteins and revealed its requirement for mitochondrial biogenesis and functional interdependence with MOM22.

    Evidence Gene disruption/RIP in yeast and Neurospora, in vitro import assays, biogenesis phenotyping

    PMID:8120088 PMID:8132642

    Open questions at the time
    • Did not separate direct receptor role from indirect biogenesis effects
    • Mechanism of MOM19-MOM22 cooperation unresolved
  4. 1995 High

    Defined the co-receptor logic by showing MOM19/MOM22 jointly bind preproteins through reversible electrostatic interactions and confirmed human TOMM20 functionally substitutes for the yeast receptor.

    Evidence Outer-membrane vesicle binding, cross-linking, antibody inactivation; human orthologue complementation in yeast

    PMID:7556061 PMID:7589431

    Open questions at the time
    • Did not resolve the structural binding mode despite implicating electrostatics
    • Order of receptor engagement during import unresolved
  5. 1999 High

    Dissected the division of labor among the three TOM receptors and mapped which preprotein segments each binds, distinguishing Tom20's presequence preference from Tom70's internal-signal preference.

    Evidence Purified recombinant cytosolic domains, in vitro binding, salt/competition and cellulose-bound peptide scans

    PMID:10347216 PMID:9252394

    Open questions at the time
    • Did not establish kinetics of substrate handoff between receptors
    • Did not resolve atomic binding geometry
  6. 1999 High

    Revealed a Tom40-pore-independent function: Tom20 alone can insert VDAC into lipid bilayers, expanding its role beyond presequence import.

    Evidence Reconstituted liposomes with hTom20 cytosolic domain, ts-Tom40 mutant mitochondria, ATP transport readout

    PMID:10352015

    Open questions at the time
    • Physiological contribution of this pathway versus the SAM/Tom40 route unclear
    • Structural basis of β-barrel insertion by Tom20 unresolved
  7. 2000 High

    Provided the structural mechanism of presequence recognition, showing an all-α-helical domain binds presequences as amphiphilic helices primarily through hydrophobic contacts.

    Evidence NMR structure of rat Tom20 bound to an aldehyde dehydrogenase presequence, peptide binding; TMD targeting determinant mutagenesis

    PMID:10721992 PMID:11038175 PMID:9218491

    Open questions at the time
    • Reconciliation of hydrophobic binding with the known importance of positive charge incomplete
    • Single static structure did not capture binding dynamics
  8. 2007 High

    Resolved how a low-specificity groove recognizes diverse presequences by demonstrating a dynamic multi-pose binding equilibrium, and established that Mim1 catalyzes Tom20 TMD docking into the complex.

    Evidence Crystal structures with disulfide-tethered presequences, NMR 15N relaxation; Tom20 TMD and Mim1 deletion mutagenesis

    PMID:11237589 PMID:17948058 PMID:18063580 PMID:18177669 PMID:18187149

    Open questions at the time
    • Functional consequence of the dynamic equilibrium for translocation rate unresolved
    • How TMD docking couples to receptor activity not mechanistically defined
  9. 2010 High

    Extended Tom20 function to mRNA biology and to a two-element import mechanism, showing it localizes mitochondrial mRNAs translation-dependently and uses distinct presequence elements for targeting versus efficiency.

    Evidence Mitochondrial fractionation with microarray mRNA profiling, genetic epistasis, polysome analysis; NMR mapping with in vitro import

    PMID:19858288 PMID:21173275

    Open questions at the time
    • Whether mRNA localization is direct or via co-translational import-driven tethering unresolved
    • Adaptor connecting Tom20 to mRNA not identified
  10. 2011 Medium

    Characterized inter-receptor coordination and supramolecular organization, mapping the Tom20-Tom70 DDVE interaction implicated in chaperone displacement and showing Tom20 forms membrane-potential-dependent nanoclusters.

    Evidence Cross-linking on native mitochondria, co-precipitation, NMR titration, SPR; super-resolution STED cluster analysis

    PMID:21771790 PMID:21799113

    Open questions at the time
    • Functional role of nanoclustering in import throughput unresolved
    • Mechanism linking membrane potential to cluster density unknown
  11. 2016 High

    Connected TOMM20 to disease and to ubiquitin-mediated turnover, showing pathogenic α-synuclein blocks the TOM20-TOM22 interaction to impair import and that SCF-Fbxo7 ubiquitinates TOMM20 to promote mitophagy.

    Evidence Co-IP, in vitro import, respiration/ROS/potential measurements, PD brain tissue and in vivo knockdown; protein array screen and ubiquitination assays

    PMID:27280685 PMID:27503909

    Open questions at the time
    • The α-synuclein modification responsible in vivo and its prevalence not fully defined
    • Fbxo7 ubiquitination chain topology and downstream mitophagy effector not fully mapped
  12. 2018 High

    Defined a cell-death function in which oxidized, oligomerized Tom20 recruits Bax to drive caspase-3/GSDME pyroptosis, linking the receptor to redox-triggered programmed death.

    Evidence Co-IP, siRNA knockdown, pathway immunoblotting, xenograft tumor model

    PMID:30287942

    Open questions at the time
    • Structural basis of redox-induced oligomerization and Bax recruitment unresolved
    • Generality beyond melanoma not established
  13. 2021 Medium

    Demonstrated that Tom20 is a dynamically, not statically, associated TOM subunit and that it controls Bcl2 delivery to mitochondria, integrating import-complex dynamics with apoptotic regulation.

    Evidence Single-particle tracking with intein-mediated ligation control; subcellular fractionation, co-IP, domain mapping, yeast ERMES model

    PMID:33589622 PMID:34347503

    Open questions at the time
    • Bcl2 transfer mechanism through MAM not mechanistically detailed (single lab)
    • Quantitative link between Tom20 mobility and import flux incomplete
  14. 2022 High

    Cryo-EM of the human and Neurospora TOM holo complexes placed Tom20 within the assembled translocase as a dynamic gatekeeper and revealed shared three-helix-bundle architecture with Tom22 contacting preprotein at the pore.

    Evidence Single-particle cryo-EM at multiple resolutions with structure-guided mutagenesis and preprotein-bound states

    PMID:35733257 PMID:37579144

    Open questions at the time
    • Limited resolution of the Tom20 receptor density left side-chain detail of the holo arrangement incomplete
    • Dynamics of gating not captured in static maps
  15. 2024 High

    Established Tom20 as a stress-signaling and regulatory hub: PINK1 tethers TOM to TIM23 via the Tom20 cytosolic domain to license mitophagy, HUWE1 directly ubiquitinates TOMM20, and a single central Tom20 was resolved in the human holo complex.

    Evidence Co-IP, native gels, PINK1/Tom20 mutagenesis in iPSC dopamine neurons and organoids; ubiquitination assays; cross-linking-stabilized cryo-EM

    PMID:38184713 PMID:38416681 PMID:39071881

    Open questions at the time
    • How PINK1 docking is coupled to TIM23 supercomplex assembly mechanistically incomplete
    • HUWE1 versus Fbxo7 versus PARKIN division of labor in TOMM20 turnover unresolved
  16. 2025 Medium

    Expanded the regulatory and iron-handling roles of TOMM20, showing it recruits FEM1B-CRL2 to degrade PLD6 controlling mitochondrial dynamics, stabilizes androgen receptor in prostate cancer, and forms a PCBP2-TOM20-SFXN3 axis for mitochondrial iron entry.

    Evidence Proteomics, structural/biochemical analysis, co-IP, GST pulldown, ubiquitination, ChIP/RNA-seq, proximity ligation and iron measurements

    PMID:38599240 PMID:40044984 PMID:40263465

    Open questions at the time
    • Each function rests on single-lab evidence with limited mechanistic depth
    • Whether these moonlighting roles depend on Tom20's import-receptor activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Tom20's dynamic presequence binding, lateral mobility within the TOM complex, and its diverse non-import roles (mRNA tethering, VDAC insertion, signaling-platform functions) are coordinated into a single regulated cycle remains unresolved.
  • No unified model linking receptor dynamics to throughput control
  • Hierarchy and crosstalk among the multiple E3 ligases governing TOMM20 levels undefined
  • Physiological weighting of canonical import versus moonlighting functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0038024 cargo receptor activity 3 GO:0140104 molecular carrier activity 3 GO:0060089 molecular transducer activity 2 GO:0044183 protein folding chaperone 1
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-9609507 Protein localization 3 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
AIPFBXO7FEM1BHUWE1PINK1TOMM22TOMM40TOMM70
Complex memberships
TOM complex (mitochondrial outer membrane translocase)

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 MOM19 (TOMM20) is a 19 kDa mitochondrial outer membrane protein that functions as an import receptor; IgG and Fab fragments against MOM19 inhibit high-affinity binding and import of precursor proteins destined for multiple mitochondrial subcompartments (matrix, inner membrane, intermembrane space), but not ADP/ATP carrier or cytochrome c. Antibody inhibition of in vitro mitochondrial protein import; immunoprecipitation Cell High 2557158
1991 MOM19 is anchored in the outer mitochondrial membrane via an NH2-terminal hydrophobic sequence with the rest forming a cytosolic hydrophilic domain; its targeting to mitochondria is independent of protease-accessible surface receptors and occurs via direct assembly with the general insertion site (GIP). Gene cloning, sequence analysis, in vitro targeting assays, protease protection Science High 1661031
1994 Deletion of MOM19 (yeast TOMM20) strongly impairs import of cleavable preproteins but only slightly inhibits import of non-cleavable ADP/ATP carrier and phosphate carrier, establishing MOM19 as the primary receptor for presequence-containing preproteins. Gene disruption (delta MOM19 yeast), in vitro protein import assays, in vivo precursor accumulation The Journal of biological chemistry High 8132642
1994 Depletion of MOM19 in Neurospora crassa causes severe mitochondrial biogenesis defects including loss of cristae, reduced cytochromes, and impaired protein import; additionally, loss of MOM19 leads to decreased MOM22 levels and reduced import through MOM22, revealing a functional interdependence. Sheltered RIP mutagenesis, protein import into isolated mutant mitochondria, Western blot The Journal of cell biology High 8120088
1995 MOM22 and MOM19 cooperate as a presequence receptor complex at the mitochondrial surface; both bind preproteins in a reversible, salt-sensitive manner dependent on electrostatic interactions between presequence positive charges and MOM22's acidic cytosolic domain; MOM19 and MOM22 can be cross-linked with high efficiency. Purified outer membrane vesicle binding assays, cross-linking, antibody inactivation The EMBO journal High 7556061
1995 Human TOMM20 (huMas20p) is inserted into the outer mitochondrial membrane in Nin-Ccyto orientation, can functionally complement delta mas20 yeast respiratory defects, and antibodies against its soluble domain inhibit import of diverse precursor proteins including uncoupling protein. In vitro import into isolated rat heart mitochondria, yeast complementation, antibody inhibition assays FEBS letters High 7589431
1997 Purified cytosolic domains of Tom20, Tom22, and Tom70 each bind mitochondrial preproteins independently but with different specificities: Tom20 binds both presequence-containing and internal-signal preproteins; Tom22 selectively binds presequence preproteins in a salt-sensitive manner; Tom70 preferentially binds preproteins with internal targeting information. A synthetic presequence peptide competes for Tom20 and Tom22 but not Tom70 binding. Recombinant cytosolic domain expression/purification, in vitro binding assays, salt/competition experiments The Journal of biological chemistry High 9252394
1997 The linker segment (charged amino acid-rich region between the membrane anchor and TPR motif) of rat Tom20 is essential for its receptor function; the TPR motif and C-terminal acidic cluster are dispensable. Tom20N69 (anchor + linker only) complements delta tom20 yeast growth and import defects. Truncation mutagenesis, complementation of delta tom20 yeast, in vitro import assays The Journal of biological chemistry High 9218491
2000 NMR structure of rat Tom20 cytosolic domain in complex with an aldehyde dehydrogenase presequence reveals an all alpha-helical structure with a hydrophobic groove accommodating the presequence as an amphiphilic helix; binding is mediated mainly by hydrophobic rather than ionic interactions despite the importance of positive charges for import. NMR structure determination, peptide binding assays Cell High 10721992
2000 The mitochondrial targeting signal of Tom20 requires moderate TMD hydrophobicity and a net positive charge within five residues of the COOH-terminal flanking region; high TMD hydrophobicity or loss of positive charges redirects Tom20 to the ER-Golgi. SRP recognizes the TMD but with reduced affinity; the positive COOH-terminal charge inhibits SRP-induced translation arrest. GFP fusion constructs with deletion/mutation analysis in COS-7 cells, fluorescence microscopy, cell fractionation, SRP photo-cross-linking The Journal of cell biology High 11038175
1999 Tom20, Tom22, and Tom70 cytosolic domains bind to linear peptide segments of preproteins with differential specificity: Tom20 preferentially binds presequence segments; Tom22 binds the C-terminal presequence/N-terminal mature protein junction; Tom70 and Tom20 both bind multiple internal regions of non-cleavable carriers (phosphate carrier), whereas charge is not a critical determinant for internal targeting sequences. Cellulose-bound peptide scan binding assays with purified recombinant receptor domains The Journal of biological chemistry High 10347216
1999 Tom20 directly inserts newly synthesized VDAC into lipid bilayers as a functional transmembrane channel, bypassing the Tom40 translocation pore; synthetic liposomes containing only the cytosolic domain of human Tom20 are sufficient for this insertion activity. In vitro VDAC insertion assay with Tom40 pore-plugging, temperature-sensitive Tom40 mutant mitochondria, reconstituted liposomes with hTom20, ATP transport assay The Journal of cell biology High 10352015
2001 Tom20 binds different segments (N-terminal or C-terminal regions) in different presequences; the binding is mediated by hydrophobic interactions and the bound presequence orientation is the same regardless of which segment is perturbed. NMR chemical shift perturbation with 15N-labeled presequence peptides; spin-label experiments Journal of molecular biology High 11237589
2003 AIP (arylhydrocarbon receptor-interacting protein) binds to the COOH-terminal acidic segment of Tom20 via its TPR domain and forms a ternary complex with Tom20 and mitochondrial preproteins; AIP has chaperone-like activity that prevents preproteins from losing import competency. Yeast two-hybrid, in vitro import assay, RNAi knockdown in cultured cells, in vitro binding assay, aggregation suppression assay The Journal of cell biology High 14557246
2003 The cytosolic domains of Tom20 and Tom22 possess chaperone-like activity that prevents substrate proteins from aggregating; Tom20 binds unfolded substrate proteins regardless of presequence presence, and a presequence peptide inhibits this chaperone activity, suggesting the presequence-binding and chaperone-active sites are identical or adjacent. In vitro aggregation suppression assays (citrate synthase), competitive inhibition with presequence peptide, in vitro binding with guanidinium-unfolded substrates The Journal of biological chemistry Medium 14699115
2007 Tom20 recognizes mitochondrial presequences through dynamic equilibrium among multiple bound states (multiple-mode interaction); crystal structures with disulfide-tethered presequences show two unique relative orientations of the presequence, and NMR 15N relaxation analyses indicate sub-millisecond timescale motion at the Tom20-presequence interface. X-ray crystallography (two crystal forms with disulfide tethering), NMR 15N relaxation analysis The EMBO journal High 17948058
2007 Tom20 and Tom22 are involved in the same step or sequential steps of the same targeting signal recognition pathway; selective protease cleavage of either receptor domain causes similar import impairment across multiple substrate classes and import pathways. In vitro protease cleavage of receptor domains via engineered TEV protease sites; in vitro protein import assays with defined substrates The Journal of biological chemistry High 18063580
2007 The transmembrane segment of Tom20 contains critical residues required for its docking into the TOM complex; this docking is catalyzed by the assembly factor Mim1/Tom13. Mutations destabilizing the TMD or deletion of Mim1 prevent Tom20 from functioning as an import receptor. Mutagenesis of Tom20 TMD, genetic deletion of Mim1, in vitro/in vivo import assays Journal of molecular biology High 18187149
2007 Mim1 is required for integration of Tom20 into the outer mitochondrial membrane; Mim1 functions as a homo-oligomer via GXXXG dimerization motifs in its transmembrane segment; mutations in the GXXXG motifs abolish oligomerization and Mim1 function, preventing Tom20 membrane integration. In vivo and in vitro integration assays, mutagenesis of GXXXG motifs, co-immunoprecipitation Journal of molecular biology High 18177669
2010 Tom20 mediates localization of mRNAs encoding mitochondrial proteins to the mitochondrial surface in a translation-dependent manner requiring features within the encoded mitochondrial targeting signal; tom20Δ yeast show reduced mitochondrial association of most mitochondrial mRNAs, and tom20Δ puf3Δ double knockouts show additive growth defects. Mitochondrial fractionation, DNA microarray mRNA profiling, genetic epistasis (double knockout), polysome analysis Molecular and cellular biology High 19858288
2010 Tom20 has a dual role in mitochondrial protein import: an N-terminal binding element in the presequence is essential for mitochondrial targeting specificity, while a C-terminal element increases import efficiency at a step prior to inner membrane translocation, revealed by NMR mapping and in vitro import/cross-linking experiments. NMR chemical shift perturbation, in vitro import assays, cross-linking Proceedings of the National Academy of Sciences High 21173275
2011 Tom20 interacts with the TPR clamp domain of Tom70 via a conserved C-terminal DDVE motif, as shown by cross-linking on mitochondria from HeLa cells and co-precipitation/NMR with purified proteins; Tom20 competes with Hsp70/Hsp90 for Tom70 binding, suggesting a chaperone displacement mechanism for preprotein release from Tom70. Chemical cross-linking on native mitochondria, co-precipitation, NMR titration, SPR (Hsp90-Tom70 interaction), DDVE motif deletion mutagenesis The Journal of biological chemistry High 21771790
2011 Tom20 is distributed in nanoscale clusters in the outer mitochondrial membrane; cluster density correlates with mitochondrial membrane potential and follows an inner-cellular gradient from perinuclear to peripheral mitochondria, adjusted to cellular growth conditions. Super-resolution STED microscopy in >1000 cells, quantitative cluster analysis Proceedings of the National Academy of Sciences Medium 21799113
2016 Posttranslationally modified α-synuclein binds with high affinity to the TOM20 presequence receptor, preventing TOM20-TOM22 co-receptor interaction and impairing mitochondrial protein import; this results in deficient respiration, elevated ROS, and loss of membrane potential. Modest knockdown of α-synuclein maintained import in a PD model; TOM20 overexpression preserved import. Co-immunoprecipitation, in vitro import assays, mitochondrial respiration/ROS/membrane potential measurements, postmortem PD brain tissue analysis, in vivo α-synuclein knockdown model Science translational medicine High 27280685
2016 SCFFbxo7/PARK15 ubiquitin ligase ubiquitinates TOMM20, and TOMM20 ubiquitination promotes mitophagy; TOMM20 protein levels correlate with Fbxo7 expression (stabilizing effect). PD-associated Fbxo7 mutations do not impair TOMM20 ubiquitination. Protein array high-throughput screen, in vitro and in vivo ubiquitination assays, ubiquitin chain restriction analysis The Biochemical journal Medium 27503909
2018 ROS-induced oxidation and oligomerization of Tom20 enables Bax recruitment to mitochondria; oxidized Tom20 facilitates cytochrome c release to activate caspase-3, which then cleaves GSDME to trigger pyroptosis. This Tom20-Bax-caspase-GSDME pathway mediates iron-driven pyroptotic cell death in melanoma cells. Co-immunoprecipitation, siRNA knockdown of Tom20, Western blot for pathway components, xenograft tumor model Cell research High 30287942
2019 Celastrol blocks PINK1-dependent mitophagy by disrupting the direct association between PINK1 and TOM20 both in vitro and in vivo; PINK1 directly and strongly associates with TOM20 (and more weakly with TOM70); celastrol also disrupts PINK1 complex formation and sequesters PINK1 into high-molecular-weight aggregates upon mitochondrial depolarization. Recombinant protein binding assay, kinase assay, immunoblotting, immunofluorescence live-cell imaging, native gel analysis The Journal of biological chemistry Medium 30885942
2021 Tom20 controls the mitochondrial localization of Bcl2; upon apoptosis induction, Bcl2 is translocated from ER through MAM to mitochondria, and this transfer is dependent on TOM20. A small TOM20-Bcl2 interaction domain potentiates Bcl2's anti-apoptotic properties, suggesting the TOM20-Bcl2 interaction is pro-apoptotic. Subcellular fractionation, co-immunoprecipitation, domain mapping, yeast ERMES deletion model Cell death & disease Medium 33589622
2021 Tom20 is dynamically associated with the TOM complex; single-particle tracking in human cells shows Tom20 has higher lateral membrane mobility than Tom7/TOM core. Post-translational ligation of Tom20 to Tom7 (reducing Tom20 mobility) or high substrate loading both decrease Tom20 diffusion, suggesting dynamic association is functionally relevant for active import. Single-particle tracking of labeled Tom20, post-translational protein trans-splicing (Gp41-1 intein), diffusion coefficient measurements Molecular biology of the cell Medium 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 structural feature in the cytosolic domain; structure-guided mutagenesis shows the Tom22 cytosolic domain H1 helix is critical for presequence binding. Cryo-EM structure determination, structure-guided mutagenesis, biochemical presequence-binding assays Proceedings of the National Academy of Sciences High 35733257
2023 Cryo-EM structures of the TOM core complex (3.3 Å) and holo complex including Tom20 (6-7 Å) from Neurospora crassa reveal Tom20 has a transmembrane helix and cytoplasmic receptor domain and acts as a dynamic gatekeeper; the structure shows Tom20 interactions with other TOM subunits and a bound preprotein, supporting a dynamic gating mechanism for preprotein entry into the pore. Single-particle cryo-EM (3.3 Å core, 4 Å with preprotein, 6-7 Å holo complex) Proceedings of the National Academy of Sciences High 37579144
2024 Upon mitochondrial stress, PINK1 forms a supercomplex with TOM and TIM23 in human cells, dopamine neurons, and midbrain organoids; PINK1 tethers TOM to TIM23 through an interaction between the PINK1 N-terminal-C-terminal extension module and the cytosolic domain of Tom20. Disruption of this interaction (by designer or PD-associated PINK1 mutations) inhibits downstream mitophagy. Co-immunoprecipitation, native gel analysis, PINK1 mutagenesis, human iPSC-derived dopamine neurons, midbrain organoids, mitophagy assays Proceedings of the National Academy of Sciences High 38416681
2024 Cryo-EM structure of the human TOM holo complex (∼6 Å) reveals the intact Tom20 receptor, showing only one Tom20 subunit at the center of the complex stabilized by extensive interactions with Tom22, Tom40, and Tom6; the structure suggests different receptors can work simultaneously for efficient preprotein translocation. Chemical cross-linking to stabilize Tom20, cryo-EM structure determination PNAS nexus High 39071881
2024 HUWE1 E3 ubiquitin ligase directly ubiquitinates TOMM20 and regulates its degradation; HUWE1 also regulates TOMM20 degradation via the PARKIN-mediated pathway. HUWE1 overexpression impairs mitochondrial function (ATP generation, membrane potential), increases ROS and apoptosis, sensitizing CRC cells to oxaliplatin. Co-immunoprecipitation, in vitro ubiquitination assay, HUWE1 overexpression/knockdown, mitochondrial functional assays Oncogene Medium 38184713
2025 FEM1B (substrate receptor of CRL2 E3 ligase) physically interacts with TOM20, and this interaction facilitates FEM1B-mediated ubiquitination and degradation of PLD6, a regulator of mitochondrial dynamics. Disruption of the FEM1B-TOM20 interaction impairs PLD6 degradation and causes mitochondrial morphology defects phenocopying PLD6 overexpression. Proteomic analysis, structural and biochemical approaches, co-immunoprecipitation, FEM1B/TOM20 interaction mutagenesis, PLD6 degradation assays, mitochondrial morphology analysis Nature chemical biology High 40263465
2025 TOMM20 physically interacts with androgen receptor (AR) and stabilizes AR protein in prostate cancer cells; TOMM20 depletion reduces cytoplasmic and nuclear AR protein levels and promotes AR degradation via the SKP2-mediated ubiquitin-proteasome pathway, independently of heat shock proteins; TOMM20 knockdown reduces AR binding to androgen response elements and AR-target gene transcription. Co-immunoprecipitation, GST pull-down, RNA-seq, ChIP assay, Western blot, ubiquitination assay Oncogene Medium 40044984
2024 TOM20 directly binds sideroflexin-3 (SFXN3) in the mitochondrial outer membrane, and proximity ligation assay shows PCBP2 (cytosolic Fe(II) chaperone) is proximal to TOM20 at the mitochondrial surface; this establishes a PCBP2-TOM20-SFXN3 axis as a pathway for iron entry into mitochondria. GST pulldown/LC-MS, co-immunoprecipitation, proximity ligation assay, STED microscopy, SFXN3/PCBP2 knockdown/knockout with mitochondrial iron and respiration measurements Free radical research Medium 38599240

Source papers

Stage 0 corpus · 91 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 533 30287942
2016 α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease. Science translational medicine 494 27280685
2000 Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 460 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 197 10347216
2000 Characterization of the signal that directs Tom20 to the mitochondrial outer membrane. The Journal of cell biology 180 11038175
2010 Tom20 mediates localization of mRNAs to mitochondria in a translation-dependent manner. Molecular and cellular biology 144 19858288
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 135 21799113
2007 Tom20 and Tom22 share the common signal recognition pathway in mitochondrial protein import. The Journal of biological chemistry 133 18063580
2007 Tom20 recognizes mitochondrial presequences through dynamic equilibrium among multiple bound states. The EMBO journal 128 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 94 21173275
2007 Mim1 functions in an oligomeric form to facilitate the integration of Tom20 into the mitochondrial outer membrane. Journal of molecular biology 92 18177669
2007 The transmembrane segment of Tom20 is recognized by Mim1 for docking to the mitochondrial TOM complex. Journal of molecular biology 92 18187149
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
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 63 38416681
1999 Direct membrane insertion of voltage-dependent anion-selective channel protein catalyzed by mitochondrial Tom20. The Journal of cell biology 57 10352015
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 56 35733257
1995 A human homolog of the mitochondrial protein import receptor Mom19 can assemble with the yeast mitochondrial receptor complex. FEBS letters 56 7498524
2021 TOM20-mediated transfer of Bcl2 from ER to MAM and mitochondria upon induction of apoptosis. Cell death & disease 53 33589622
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
2010 Recognition of mitochondrial targeting sequences by the import receptors Tom20 and Tom22. Journal of molecular biology 50 21087612
2011 Interaction between the human mitochondrial import receptors Tom20 and Tom70 in vitro suggests a chaperone displacement mechanism. The Journal of biological chemistry 48 21771790
1998 Functional and structural properties of the mitochondrial outer membrane receptor Tom20. Biochemistry 46 9748309
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 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
2016 Gsk3β and Tomm20 are substrates of the SCFFbxo7/PARK15 ubiquitin ligase associated with Parkinson's disease. The Biochemical journal 42 27503909
2003 Mitochondrial import receptors Tom20 and Tom22 have chaperone-like activity. The Journal of biological chemistry 42 14699115
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
2021 The receptor subunit Tom20 is dynamically associated with the TOM complex in mitochondria of human cells. Molecular biology of the cell 32 34347503
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
2006 Prevention of the ischemia-induced decrease in mitochondrial Tom20 content by ischemic preconditioning. Journal of molecular and cellular cardiology 29 16828795
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 28 32920118
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 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 24 9748310
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 23 37579144
2012 Immunocytochemical localization of the translocase of the outer mitochondrial membrane (Tom20) in the human cochlea. Anatomical record (Hoboken, N.J. : 2007) 22 23165776
2009 Mitochondrial targeting of cytochrome P450 proteins containing NH2-terminal chimeric signals involves an unusual TOM20/TOM22 bypass mechanism. The Journal of biological chemistry 21 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
2023 Hsp70-Bim interaction facilitates mitophagy by recruiting parkin and TOMM20 into a complex. Cellular & molecular biology letters 17 37237369
1999 Gene structure of the human mitochondrial outer membrane receptor Tom20 and evolutionary study of its family of processed pseudogenes. Gene 17 10548729
2023 AR antagonists develop drug resistance through TOMM20 autophagic degradation-promoted transformation to neuroendocrine prostate cancer. Journal of experimental & clinical cancer research : CR 15 37563661
2021 PRR34-AS1 sponges miR-498 to facilitate TOMM20 and ITGA6 mediated tumor progression in HCC. Experimental and molecular pathology 14 33609562
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 13 35269514
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
2024 Neobractatin induces pyroptosis of esophageal cancer cells by TOM20/BAX signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 12 38547615
2025 TOM20-driven E3 ligase recruitment regulates mitochondrial dynamics through PLD6. Nature chemical biology 10 40263465
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
2024 Structure of the intact Tom20 receptor in the human translocase of the outer membrane complex. PNAS nexus 9 39071881
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
2023 Endogenous TOM20 Proximity Labeling: A Swiss-Knife for the Study of Mitochondrial Proteins in Human Cells. International journal of molecular sciences 7 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
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 TOMM20 as a driver of cancer aggressiveness via oxidative phosphorylation, maintenance of a reduced state, and resistance to apoptosis. Molecular oncology 3 39996379
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 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
2026 The role of TOMM20 in Mediating TERT translocation to mitochondria and its impact on mitophagy in membranous nephropathy. BMC nephrology 0 41922997
2026 CSDE1 Associates with TOM20 and Mitochondrial Protein-Encoding mRNAs in Sensory Neurons. Antioxidants (Basel, Switzerland) 0 42193230
2025 GATA-1-driven TOMM20-mediated mitophagy regulates PDLSCs osteogenesis and enhances periodontal bone regeneration. Biochemical and biophysical research communications 0 41389613

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