Affinage

USP30

Ubiquitin carboxyl-terminal hydrolase 30 · UniProt Q70CQ3

Length
517 aa
Mass
58.5 kDa
Annotated
2026-06-11
66 papers in source corpus 24 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP30 is a mitochondrial outer membrane-anchored deubiquitinase that regulates mitochondrial morphology and quality control by reversing ubiquitin signals on outer-membrane proteins (PMID:18287522, PMID:24896179). It opposes PINK1/Parkin-driven mitophagy: USP30 removes ubiquitin from Parkin substrates on damaged mitochondria and blocks their degradation, while its loss enhances mitophagic flux and rescues defective mitophagy in Drosophila Parkin mutants (PMID:24896179). Mechanistically, USP30 deubiquitylates components of the TOM translocon, including TOM20 and TOMM40, thereby dampening the local ubiquitin signal at sites of PINK1 accumulation and setting a trigger threshold for Parkin-dependent amplification (PMID:25739811, PMID:32636217); in neurons its loss causes ubiquitylated translocon import substrates to accumulate, defining a quality-control function at the TOM complex (PMID:32142685). Crystal structures of USP30 bound to monoubiquitin and Lys6-linked diubiquitin reveal ubiquitin-binding interfaces that confer Lys6-linkage cleavage preference, and distally pSer65-phosphorylated ubiquitin chains impair USP30 activity (PMID:28945249). Beyond translocon control, USP30 deubiquitylates and tunes the activity or stability of mitochondrial dynamics factors (Mfn1/2, DRP1), regulates the BAX/BAK-dependent apoptotic threshold, and counteracts the peroxisomal E3 ligase PEX2 to suppress basal pexophagy, giving it a dual organelle role (PMID:24513856, PMID:25739811, PMID:30143522, PMID:30700497). CDK5 phosphorylates USP30 at Ser216 to stabilize the protein and suppress mitophagy (PMID:38772138). In non-mitochondrial contexts USP30 stabilizes additional substrates including Snail, FTO, MAT2A, NLRP3 and HK1/2 to influence EMT, serine biosynthesis, methylation, inflammasome activity and glycolysis (PMID:34883112, PMID:38146008, PMID:41652187, PMID:41688443, PMID:41104980). USP30 is an actively pursued drug target, with multiple inhibitor classes mapped to distinct binding modes near the catalytic and ubiquitin-binding sites (PMID:37385347, PMID:40325251, PMID:39804742).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2008 High

    Established that USP30 is an outer-membrane deubiquitinase whose catalytic activity controls mitochondrial morphology, answering what cellular process this DUB governs.

    Evidence RNAi knockdown with wild-type vs catalytic-dead rescue and mitochondrial morphology imaging

    PMID:18287522

    Open questions at the time
    • Substrates mediating the morphology phenotype not identified
    • Link to mitophagy not yet established
  2. 2014 High

    Defined USP30 as an antagonist of Parkin-mediated mitophagy and identified mitochondrial substrates oppositely regulated by Parkin, explaining how it counteracts mitochondrial clearance.

    Evidence Overexpression/knockdown, global ubiquitination site proteomics, and Drosophila genetic rescue of pathogenic Parkin mutants

    PMID:24896179

    Open questions at the time
    • Linkage specificity of cleaved chains not yet resolved
    • Direct vs indirect deubiquitylation of each profiled substrate unclear
  3. 2014 Medium

    Showed that USP30 deubiquitylation of mitofusins suppresses their fusion activity, mechanistically connecting USP30 to mitochondrial fusion.

    Evidence Chemical inhibition by 15-oxospiramilactone with Mfn1/2 ubiquitination and fusion assays in Mfn-deficient lines

    PMID:24513856

    Open questions at the time
    • Inhibitor selectivity beyond USP30 not fully excluded
    • Direct enzymatic action on Mfn chains not reconstituted
  4. 2015 Medium

    Connected USP30 to the apoptotic threshold by showing TOM20 deubiquitylation and modulation of BAX/BAK-dependent cell death, extending its role beyond morphology.

    Evidence siRNA/shRNA depletion, TOM20 ubiquitylation assays, and BH3-mimetic sensitivity assays

    PMID:25739811

    Open questions at the time
    • Molecular link between TOM20 deubiquitylation and BAX/BAK control not defined
    • Single-lab apoptosis phenotype
  5. 2017 High

    Provided the structural basis for USP30's Lys6-linkage preference and its inhibition by pSer65-ubiquitin, explaining substrate-chain selectivity and PINK1 cross-regulation.

    Evidence X-ray crystallography of mono- and Lys6-diubiquitin complexes, in vitro DUB assays, and Lys6-specific affimer pulldowns

    PMID:28945249

    Open questions at the time
    • In vivo prevalence of Lys6 chains on substrates not quantified
    • Full substrate repertoire of Lys6 cleavage unknown
  6. 2018 High

    Revealed a dual-organelle role by showing peroxisomal USP30 suppresses basal pexophagy and acts upstream of PINK1 in basal mitophagy, broadening its quality-control scope.

    Evidence Mitophagy/pexophagy reporters, peroxisomal localization by fractionation/imaging, and genetic perturbation

    PMID:29895712

    Open questions at the time
    • Peroxisomal substrates not identified in this study
    • Mechanism of dual targeting between organelles unclear
  7. 2018 Medium

    Identified DRP1 as a USP30 substrate recruited via GNPAT, linking USP30-driven fission to hepatocarcinogenesis.

    Evidence Co-IP, DRP1 ubiquitination and stability assays, and loss-of-function in HCC cells

    PMID:30143522

    Open questions at the time
    • Reciprocal validation of GNPAT-USP30 complex limited
    • Chain linkage on DRP1 not defined
  8. 2019 High

    Defined a PEX2–USP30 ubiquitin axis controlling peroxisome abundance, establishing the E3 ligase USP30 opposes at peroxisomes.

    Evidence USP30 overexpression/depletion, pexophagy assays, peroxisomal imaging, and genetic epistasis with PEX2

    PMID:30700497

    Open questions at the time
    • Specific PEX2-generated substrate chains not enumerated
    • Relative contribution of mitochondrial vs peroxisomal pools unresolved
  9. 2020 High

    Showed in physiological neurons that USP30 acts as a quality-control DUB at the TOM translocon, concentrating its effect on import substrates rather than the bulk Parkin target set.

    Evidence Quantitative ubiquitylomics in CRISPR USP30-/- iNeurons with mitophagy flux assays

    PMID:32142685

    Open questions at the time
    • Modest mitophagy effect leaves physiological magnitude uncertain
    • Mechanism distinguishing translocon substrates unclear
  10. 2020 High

    Established that USP30 sets a trigger threshold by deubiquitylating TOM complex components to slow PINK1/Parkin amplification, with TOM20 ubiquitylation as a readout of USP30 loss.

    Evidence Selective inhibitor FT3967385 vs genetic KO comparison with proteomics and pS65-Ub kinetics in SH-SY5Y

    PMID:32636217

    Open questions at the time
    • Threshold-setting model not tested in vivo
    • Quantitative kinetics of signal amplification not modeled
  11. 2020 Medium

    Mapped an active-site residue (W475) governing diubiquitin linkage selectivity, refining the determinants of K6-specificity.

    Evidence Genetic code expansion with noncanonical Trp analogues, in vitro diubiquitin DUB assays, and crystallography

    PMID:32484330

    Open questions at the time
    • Engineered residues not physiological
    • Effect on cellular substrate selection untested
  12. 2021 Medium

    Extended USP30 substrates to NLRP3, linking it to inflammasome activation outside the mitophagy axis.

    Evidence Co-IP, ubiquitination assays, shRNA and inhibitor MF-094 with inflammasome readouts in skin fibroblasts

    PMID:34883112

    Open questions at the time
    • Single-lab substrate claim
    • Chain type and direct enzymatic action not fully defined
  13. 2022 Medium

    Identified an autoinhibitory allosteric role for the transmembrane domain, proposing a regulatory mechanism for USP30 catalytic activity.

    Evidence Q14 peptide binding by fluorescence polarization and microscale thermophoresis with mitophagy and LIR-motif characterization

    PMID:34989313

    Open questions at the time
    • Allosteric mechanism inferred rather than structurally proven
    • Physiological relevance of TM autoinhibition untested
  14. 2023 Medium

    Showed USP30 stabilizes Snail via K48-chain removal to promote EMT, adding a non-mitochondrial oncogenic substrate.

    Evidence Co-IP, ubiquitination assays, knockdown/overexpression with invasion assays in breast cancer cells

    PMID:38146008

    Open questions at the time
    • Nuclear/cytosolic site of Snail deubiquitylation unclear given USP30 membrane anchoring
    • Single-lab claim
  15. 2023 High

    Defined a benzosulfonamide inhibitor binding mode in the thumb-palm cleft that blocks ubiquitin guidance rather than occluding the active site, informing inhibitor design.

    Evidence ABPP MS selectivity, enzyme kinetics, HDX-MS, and computational docking

    PMID:37385347

    Open questions at the time
    • Cellular efficacy correlation not central to this study
    • Docking-inferred rearrangements not crystallographically confirmed here
  16. 2024 Medium

    Identified a CDK5-USP30 phosphorylation axis (Ser216) that stabilizes USP30 and suppresses mitophagy while activating MAVS inflammation in Parkinson's disease models.

    Evidence Ser216 site mapping, CDK5 inhibition, stability assays, and MPTP/MPP+ models in BV2 cells and mice

    PMID:38772138

    Open questions at the time
    • Direct CDK5 kinase action on USP30 vs indirect effect not fully separated
    • Single-lab in vivo model
  17. 2024 Medium

    Expanded the metabolic and cancer substrate set by showing USP30 stabilizes FTO (serine sensing), C/EBPβ (via NPRC), TOMM40, and S100A6 (via HMGA2).

    Evidence Co-IP, ubiquitination assays, domain mapping, mass spectrometry, and metabolic/proliferation readouts across cancer and metabolic models

    PMID:39433172 PMID:39694080 PMID:40227042 PMID:41652187

    Open questions at the time
    • Several are single-lab substrate claims with limited orthogonal validation
    • How a membrane DUB accesses these substrates not resolved
  18. 2025 High

    Provided structural and mechanistic detail on specific inhibitor engagement, including a cryptic pocket from switching-loop rearrangement and a covalent inhibitor near catalytic Cys77.

    Evidence Crystallography of chimeric USP30-inhibitor complex and HDX-MS/ABPP with covalent inhibitor USP30-I-1

    PMID:39804742 PMID:40325251

    Open questions at the time
    • In vivo selectivity and pharmacology not addressed structurally
    • Differential clinical relevance of binding modes unknown
  19. 2025 High

    Demonstrated mitophagy-independent functions: USP30 stabilizes HK1/HK2 to drive glycolysis and stabilizes MAT2A to maintain endothelial barrier function, and its loss improves mitochondrial efficiency independently of PINK1/Parkin.

    Evidence Ubiquitinomics with K144R mutagenesis and HK activity assays; EC-specific USP30 KO mice with SAM/methylation readouts; genetic and pharmacological perturbation with bioenergetic assays (one preprint)

    PMID:41104980 PMID:41688443

    Open questions at the time
    • Breadth of PINK1/Parkin-independent functions not unified
    • Mechanism of substrate access for soluble metabolic enzymes unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP30 substrate selection is partitioned between its TOM-complex quality-control role and the growing list of non-mitochondrial substrates, and how its localization permits access to cytosolic/nuclear targets, remains unresolved.
  • No unified model reconciling membrane anchoring with non-mitochondrial substrates
  • Physiological hierarchy among substrates unknown
  • Several candidate substrates rest on single-lab Co-IP evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 3
Localization
GO:0005739 mitochondrion 3 GO:0005777 peroxisome 2
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-392499 Metabolism of proteins 3
Partners
DNM1LGNPATHK2MFN1MFN2PEX2TOMM20TOMM40

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 USP30 is a deubiquitinating enzyme embedded in the mitochondrial outer membrane; depletion by RNAi induces elongated, interconnected mitochondria dependent on mitofusin activity, and this phenotype is rescued by enzymatically active USP30 but not catalytic mutants, establishing USP30 as a regulator of mitochondrial morphology through its DUB activity. RNAi knockdown, ectopic expression of wild-type vs. catalytic-dead USP30, fluorescence microscopy of mitochondrial morphology, subcellular fractionation Molecular biology of the cell High 18287522
2014 USP30 localizes to mitochondria and opposes Parkin-mediated mitophagy: overexpression of USP30 removes ubiquitin from Parkin substrates on damaged mitochondria and blocks mitophagy, while USP30 knockdown enhances mitochondrial degradation. Global ubiquitination site profiling identified multiple mitochondrial substrates oppositely regulated by Parkin and USP30. In Drosophila, USP30 knockdown rescues defective mitophagy caused by pathogenic Parkin mutations and protects dopaminergic neurons against paraquat toxicity. Overexpression/knockdown, global ubiquitination site profiling (mass spectrometry), mitophagy assays, Drosophila genetic rescue experiments Nature High 24896179
2014 The diterpenoid derivative 15-oxospiramilactone (S3) inhibits USP30, leading to non-degradative ubiquitination of Mfn1/2 that enhances mitofusin activity and promotes mitochondrial fusion, uncovering that USP30-dependent deubiquitination of mitofusins suppresses their fusion activity. Chemical inhibition with S3, mitochondrial fusion assays, ubiquitination assays for Mfn1/2, cell lines deficient in Mfn1 or Mfn2 Cell research Medium 24513856
2015 USP30 deubiquitylates TOM20 opposing Parkin-dependent ubiquitylation; USP30 depletion enhances depolarization-induced cell death in Parkin-overexpressing cells and sensitizes cancer cells to BH3-mimetics by regulating BAX/BAK-dependent apoptosis, establishing a role for USP30 in controlling the mitochondrial apoptotic threshold. USP30 depletion (siRNA/shRNA), cell death assays, ubiquitylation assays for TOM20, BH3-mimetic sensitivity assays EMBO reports Medium 25739811
2017 Crystal structures of human USP30 bound to monoubiquitin and Lys6-linked diubiquitin reveal unique ubiquitin-binding interfaces that confer Lys6-linkage preference for cleavage. Distally phosphorylated (pSer65) ubiquitin chains impair USP30 activity. Lys6-linkage-specific affimers identified TOM20 as a mitochondrial substrate for Lys6-polyubiquitination regulated by USP30. X-ray crystallography, in vitro DUB activity assays, phospho-ubiquitin chain inhibition assays, Lys6-specific affimer pulldowns, quantitative proteomics Nature structural & molecular biology High 28945249
2018 USP30 regulates basal pexophagy independently of PINK1 and Parkin: a fraction of endogenous USP30 localizes to peroxisomes where it suppresses basal pexophagy. Additionally, USP30 acts upstream of PINK1 in basal mitophagy by modulating PINK1-substrate availability, establishing dual organelle roles. Mitophagy reporter systems, immunofluorescence/fractionation to show peroxisomal localization, genetic KO/knockdown of USP30, PINK1 pathway analysis EMBO reports High 29895712
2018 GNPAT recruits USP30, which deubiquitylates and stabilizes DRP1, thereby promoting mitochondrial fission and hepatocarcinogenesis; USP30 interaction with DRP1 was established by Co-IP. Co-immunoprecipitation, ubiquitination assays, DRP1 protein stability assays, loss-of-function experiments in HCC cells Cancer research Medium 30143522
2019 USP30 localizes to peroxisomes and prevents pexophagy by counteracting the peroxisomal E3 ubiquitin ligase PEX2; USP30 overexpression blocks amino-acid-starvation-induced pexophagy, and its depletion triggers basal pexophagy, establishing a PEX2–USP30 ubiquitin axis controlling peroxisome abundance. USP30 overexpression/depletion, pexophagy assays, peroxisomal localization by microscopy, genetic epistasis with PEX2 The Journal of cell biology High 30700497
2020 In induced neurons (iNeurons), USP30 knockout reveals that elevated ubiquitylation targets concentrate on mitochondrial translocon (TOM complex) components; USP30 loss accelerates pS65-Ub accumulation and mitophagic flux modestly without altering ubiquitylation kinetics of the vast majority of Parkin targets. Basally, ubiquitylated translocon import substrates accumulate in USP30-/- iNeurons, indicating a quality control function for USP30 at the TOM complex. Quantitative ubiquitylomics/proteomics in USP30-/- iNeurons, CRISPR KO, mitophagy flux assays Molecular cell High 32142685
2020 USP30 sets a trigger threshold for PINK1-Parkin amplification of mitochondrial ubiquitylation: TOM20 ubiquitylation is a robust biomarker for USP30 loss/inhibition, and USP30 deubiquitylation of TOM complex components dampens the local ubiquitin signal at the site of PINK1 accumulation following depolarization, slowing Parkin-dependent amplification. Selective USP30 inhibitor (FT3967385), proteomics in SH-SY5Y cells, comparison of genetic KO vs chemical inhibition, pS65-Ub kinetics, mitophagy assays Life science alliance High 32636217
2020 Tryptophan residue W475 near the USP30 active site contributes to diubiquitin linkage selectivity; replacement with noncanonical Trp analogues modulates activity and K6-specificity, with 3-benzothienyl-l-alanine inducing unique K6-specificity. Genetic code expansion/noncanonical amino acid incorporation, in vitro DUB activity assays with diubiquitin substrates, X-ray crystallography of PylRS-ncAA complexes Biochemistry Medium 32484330
2021 USP30 deubiquitylates NLRP3, activating the NLRP3 inflammasome; this interaction was verified by Co-IP and ubiquitination assays, and USP30 knockdown or inhibition reduces NLRP3 inflammasome activity in skin fibroblasts. Co-immunoprecipitation, ubiquitination assays, shRNA knockdown, USP30 inhibitor MF-094, NLRP3 inflammasome activity readouts Experimental cell research Medium 34883112
2022 A peptide (Q14) derived from the transmembrane domain of USP30 inhibits USP30 via an autoinhibitory allosteric mechanism; binding sites between Q14 and USP30 were identified by fluorescence polarization and microscale thermophoresis, proposing that the TM domain can allosterically regulate USP30 catalytic activity. Fluorescence polarization, microscale thermophoresis, peptide binding studies, mitophagy assays, LC3-interaction via LIR motif characterization Autophagy Medium 34989313
2022 A benzosulfonamide inhibitor (USP30inh) binds to the cleft between the USP30 thumb and palm subdomains, preventing ubiquitin C-terminus guidance to the active site; hydrogen-deuterium exchange MS and computational docking reveal compound-induced structural rearrangements at this cleft rather than direct active-site occlusion. Activity-based protein profiling MS (selectivity against 49 DUBs), enzyme kinetics, hydrogen-deuterium exchange MS, computational docking Molecular & cellular proteomics High 37385347
2023 USP30 interacts with and deubiquitylates Snail via K48-linked polyubiquitin chains, stabilizing Snail protein and promoting EMT in breast cancer cells; verified by Co-IP and ubiquitination assays. Co-immunoprecipitation, ubiquitination assays, knockdown/overexpression, proliferation/invasion assays Cancer gene therapy Medium 38146008
2024 CDK5 phosphorylates USP30 at serine 216 to stabilize USP30 protein; CDK5-USP30 signaling suppresses mitophagy and activates MAVS-mediated inflammation in MPTP/MPP+-induced Parkinson's disease models. Phosphorylation site identification (Ser216), CDK5 inhibition experiments, USP30 protein stability assays, MAVS pathway analysis, mitophagy assays in BV2 cells and in vivo MPTP mouse model Ecotoxicology and environmental safety Medium 38772138
2024 NPRC recruits USP30 to deubiquitinate C/EBPβ at K149 (K48-linked polyubiquitination), stabilizing C/EBPβ and driving lipid metabolism reprogramming in MAFLD; the DNA-binding domain of C/EBPβ interacts with USP30, and the ANPR region of NPRC binds USP30. Proteomics, ubiquitination analysis, Co-immunoprecipitation, domain mapping experiments Metabolism: clinical and experimental Medium 39433172
2024 HMGA2 stabilizes S100A6 by recruiting USP30, inhibiting S100A6 ubiquitination/degradation; demonstrated by Co-IP and mass spectrometry in ovarian cancer cells. Co-immunoprecipitation, mass spectrometry, ubiquitination assays, rescue experiments Biochimica et biophysica acta. Molecular basis of disease Low 39694080
2024 USP30 binds to and deubiquitylates FTO, protecting it from proteasomal degradation; USP30 senses serine/glycine levels to regulate FTO stability, which in turn demethylates PHGDH/PSAT1 mRNAs promoting serine biosynthesis in colorectal cancer. Co-immunoprecipitation, ubiquitination assays, proteomic/metabolomic analyses, m6A demethylation assays Cell death and differentiation Medium 41652187
2024 USP30 deubiquitylates TOMM40, reducing its ubiquitination and stabilizing it; USP30 knockdown reduces TOMM40 protein levels and suppresses breast cancer cell proliferation and angiogenesis, establishing TOMM40 as a USP30 substrate in cancer. Co-immunoprecipitation, ubiquitination assays, knockdown experiments, cell proliferation/angiogenesis assays Journal of biochemical and molecular toxicology Medium 40227042
2025 Crystal structure of human USP30 in complex with a specific inhibitor (enabled by chimeric protein engineering) reveals that the inhibitor occupies a cryptic pocket induced by a compound-driven conformation of the USP30 switching loop; the Leu73 ubiquitin-binding site constitutes a common ligandability hotspot for USP deubiquitinases. X-ray crystallography of chimeric USP30–inhibitor complex, chimeric protein engineering strategy, structure-activity relationship analysis Nature structural & molecular biology High 40325251
2025 A cyanopyrrolidine-containing covalent inhibitor (USP30-I-1) binds tightly near the catalytic cysteine (Cys77) of USP30 in a pocket along the thumb and palm domains, preventing ubiquitin substrate binding; HDX-MS reveals structural rearrangements that differ slightly from the benzosulfonamide binding mode, providing molecular basis for differential selectivity. Enzyme kinetics, hydrogen-deuterium exchange MS, activity-based protein profiling, selectivity profiling against DUB panel Journal of proteome research High 39804742
2025 USP30 deubiquitylates and stabilizes HK1 and HK2 by preferentially removing atypical ubiquitin chains; Lys144 of HK2 is the critical regulatory site, and USP30-mediated deubiquitination enhances HK2 stability, mitochondrial localization, VDAC1 binding, and hexokinase activity to promote glycolysis and tumor progression. Co-immunoprecipitation, quantitative proteomics and ubiquitinomics, site-directed mutagenesis (K144R), HK2 activity assays, mitochondrial fractionation Cell death & disease High 41688443
2025 USP30 depletion destabilizes methionine adenosyltransferase 2A (MAT2A) through a deubiquitination-dependent mechanism, lowering SAM levels, reducing global DNA methylation, and upregulating miR-30a-5p to suppress MDM2 and NFAT5, thereby maintaining endothelial cell barrier function via a mitophagy-independent pathway. EC-specific USP30 knockout mice, LPS/ischemia-reperfusion lung injury models, ubiquitination assays for MAT2A, SAM level measurement, DNA methylation assays, miRNA expression Advanced science Medium 41104980
2025 USP30 loss or pharmacological inhibition improves mitochondrial morphology, increases membrane potential and ATP levels with decreased oxygen consumption (suggesting more efficient mitochondrial network), and these morphological changes are independent of PINK1 or Parkin. CRISPR/Cas9 KO, CRISPRi knockdown, pharmacological inhibition, mitophagy reporters, electrophysiology, mitochondrial membrane potential and ATP assays in cell lines and iPSC-derived neurons bioRxivpreprint Medium
2024 Proximity-labelling ubiquitomics (APEX2 + K-ε-GG enrichment) identifies TOMM20, FKBP8, and LETM1 as USP30-proximal substrates; LETM1 is deubiquitinated in a USP30-dependent manner as a previously undescribed candidate substrate. APEX2 proximity labelling, ubiquitin remnant (K-ε-GG) enrichment, quantitative mass spectrometry, USP30 inhibition bioRxivpreprint Low

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 690 24896179
2016 Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond. Free radical biology & medicine 265 27094585
2014 A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30. Cell research 179 24513856
2017 Mechanism and regulation of the Lys6-selective deubiquitinase USP30. Nature structural & molecular biology 178 28945249
2020 Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling. Molecular cell 169 32142685
2008 Regulation of mitochondrial morphology by USP30, a deubiquitinating enzyme present in the mitochondrial outer membrane. Molecular biology of the cell 145 18287522
2015 USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death. EMBO reports 140 25739811
2018 Dual role of USP30 in controlling basal pexophagy and mitophagy. EMBO reports 132 29895712
2020 USP30 sets a trigger threshold for PINK1-PARKIN amplification of mitochondrial ubiquitylation. Life science alliance 101 32636217
2018 Novel highly selective inhibitors of ubiquitin specific protease 30 (USP30) accelerate mitophagy. Bioorganic & medicinal chemistry letters 101 29935771
2023 Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model. Nature communications 70 37957154
2019 Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy. The Journal of cell biology 59 30700497
2018 Amplification of Glyceronephosphate O-Acyltransferase and Recruitment of USP30 Stabilize DRP1 to Promote Hepatocarcinogenesis. Cancer research 54 30143522
2021 Benchmarking a highly selective USP30 inhibitor for enhancement of mitophagy and pexophagy. Life science alliance 49 34844982
2021 Investigation of USP30 inhibition to enhance Parkin-mediated mitophagy: tools and approaches. The Biochemical journal 44 34704599
2022 Identification of an autoinhibitory, mitophagy-inducing peptide derived from the transmembrane domain of USP30. Autophagy 43 34989313
2022 USP30: Structure, Emerging Physiological Role, and Target Inhibition. Frontiers in pharmacology 42 35308234
2021 Pharmacological inhibition of USP30 activates tissue-specific mitophagy. Acta physiologica (Oxford, England) 40 33890401
2024 USP30 inhibition induces mitophagy and reduces oxidative stress in parkin-deficient human neurons. Cell death & disease 38 38225227
2021 Long non-coding RNA USP30-AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA-299-3p and thereby overexpressing PTP4A1. Oncology letters 35 33986866
2023 Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH. Translational stroke research 33 38147294
2021 MF-094, a potent and selective USP30 inhibitor, accelerates diabetic wound healing by inhibiting the NLRP3 inflammasome. Experimental cell research 30 34883112
2021 LncRNA USP30-AS1 promotes the survival of acute myeloid leukemia cells by cis-regulating USP30 and ANKRD13A. Human cell 26 34694569
2023 Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule Benzosulfonamides. Molecular & cellular proteomics : MCP 25 37385347
2021 USP30-AS1 contributes to mitochondrial quality control in glioblastoma cells. Biochemical and biophysical research communications 25 34653676
2021 USP30 protects against oxygen-glucose deprivation/reperfusion induced mitochondrial fragmentation and ubiquitination and degradation of MFN2. Aging 24 33609088
2017 Beyond Deubiquitylation: USP30-Mediated Regulation of Mitochondrial Homeostasis. Advances in experimental medicine and biology 21 29178074
2022 lncRNA USP30-AS1 sponges miR-765 and modulates the progression of colon cancer. World journal of surgical oncology 20 35260141
2022 MF-094 nanodelivery inhibits oral squamous cell carcinoma by targeting USP30. Cellular & molecular biology letters 17 36474192
2021 Deubiquitinating enzyme USP30 negatively regulates mitophagy and accelerates myocardial cell senescence through antagonism of Parkin. Cell death discovery 17 34290230
2021 Regulation of Bax-dependent apoptosis by mitochondrial deubiquitinase USP30. Cell death discovery 17 34381024
2022 Novel Imidazole Phenoxyacetic Acids as Inhibitors of USP30 for Neuroprotection Implication via the Ubiquitin-Rho-110 Fluorometric Assay: Design, Synthesis, and In Silico and Biochemical Assays. ACS chemical neuroscience 16 35417128
2023 USP30 promotes the progression of breast cancer by stabilising Snail. Cancer gene therapy 15 38146008
2022 The Mitochondrial Deubiquitinase USP30 Regulates AKT/mTOR Signaling. Frontiers in pharmacology 14 35250566
2025 An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection. PLoS pathogens 13 39777915
2025 Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30. Nature structural & molecular biology 13 40325251
2023 Chaihu Shugan Powder inhibits interstitial cells of cajal mitophagy through USP30 in the treatment of functional dyspepsia. Journal of ethnopharmacology 13 38163556
2019 New aspects of USP30 biology in the regulation of pexophagy. Autophagy 11 31356149
2024 Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30. RSC chemical biology 8 38725909
2024 CDK5-USP30 signaling pathway regulates MAVS-mediated inflammation via suppressing mitophagy in MPTP/MPP+ PD model. Ecotoxicology and environmental safety 8 38772138
2018 Organelle Turnover: A USP30 Safety Catch Restrains the Trigger for Mitophagy and Pexophagy. Current biology : CB 8 30086320
2020 Probing the Active Site of Deubiquitinase USP30 with Noncanonical Tryptophan Analogues. Biochemistry 7 32484330
2025 Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor. Journal of proteome research 6 39804742
2025 Long noncoding RNA USP30-AS1 promotes influenza A virus replication by enhancing PHB1 function. Veterinary microbiology 6 40020267
2025 USP30 inhibition augments mitophagy to prevent T cell exhaustion. Science advances 6 40815646
2024 NPRC promotes hepatic steatosis via USP30-mediated deubiquitination of C/EBPβ. Metabolism: clinical and experimental 6 39433172
2022 The intriguing role of USP30 inhibitors as deubiquitinating enzymes from the patent literature since 2013. Expert opinion on therapeutic patents 5 34743664
2019 USP30: protector of peroxisomes and mitochondria. Molecular & cellular oncology 5 31131315
2024 Exosomal lncRNA USP30-AS1 activates the Wnt/β-catenin signaling pathway to promote cervical cancer progression via stabilization of β-catenin by USP30. Biotechnology journal 4 39014929
2024 Modulation of OPC Mitochondrial Function by Inhibiting USP30 Promotes Their Differentiation. Glia 4 39601128
2025 USP30 Aggravating the Malignant Progression of Breast Cancer and Its Resistance to Tamoxifen by Inhibiting the Ubiquitination of TOMM40. Journal of biochemical and molecular toxicology 3 40227042
2025 Spotlight on USP30: structure, function, disease and target inhibition. Frontiers in pharmacology 3 40918504
2024 FOXF1 promotes ovarian cancer metastasis by facilitating HMGA2-mediated USP30-dependent S100A6 deubiquitination. Biochimica et biophysica acta. Molecular basis of disease 3 39694080
2025 The expression of the lncRNAs USP30-AS1, ELFN1-AS1, GAS8-AS1, and SNHG11 in breast cancer samples from Iranian patients from 2014 to 2019: a cross-sectional study. BMC research notes 2 39757210
2025 GNPAT/USP30 Stabilizes DRP1 Protein to Promote Mitochondrial Fission and Functional Damage in COPD Progression. The Kaohsiung journal of medical sciences 2 40709564
2025 Activation of USP30 Disrupts Endothelial Cell Function and Aggravates Acute Lung Injury Through Regulating the S-Adenosylmethionine Cycle. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41104980
2024 USP30-AS1 Suppresses Colon Cancer Cell Inflammatory Response Through NF-κB/MYBBP1A Signaling. Inflammation 2 39503963
2025 Structure-based discovery of novel non-covalent small molecule inhibitors of USP30. Journal of computer-aided molecular design 1 40274689
2025 USP30 Knockdown Drives Mitophagy and Suppresses Pyroptosis in Heart Failure by Activating the PINK1/Parkin Pathway. International heart journal 1 41320325
2025 Nuclear and cytoplasmic USP30-AS1 coordinately regulate breast cancer progression through HnRNPF/p21 and EZH2/c-Myc/p21 axes. Genes & diseases 1 41492473
2026 Targeting mitochondrial deubiquitinase USP30 to induce mitophagy in heteroplasmic mitochondrial diseases. Pharmacological reports : PR 0 41587019
2026 USP30 senses serine/glycine levels to regulate serine biosynthesis and colorectal tumorigenesis by deubiquitinating FTO. Cell death and differentiation 0 41652187
2026 USP30-mediated Deubiquitination of Hexokinase 2 controls the metabolic fate of glucose and tumor progression. Cell death & disease 0 41688443
2026 USP30-AS1 functions as a post-transcriptional amplifier of interferon signalling to drive autoimmune pathogenesis. Cell & bioscience 0 41749253
2026 USP30 alleviates intestinal ischemia-reperfusion injury by deubiquitinating MFN2 mediating the mitochondrial endoplasmic reticulum pathway. Biochemical pharmacology 0 41765114
2025 USP30-AS1 Dictates Breast Cancer Cell Fate and Chemoresistance via a miR-3646/FZD7/Wnt/β-Catenin Circuit. Current issues in molecular biology 0 41614739

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