Affinage

USP30

Ubiquitin carboxyl-terminal hydrolase 30 · UniProt Q70CQ3

Length
517 aa
Mass
58.5 kDa
Annotated
2026-04-28
66 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP30 is a mitochondrial outer membrane-anchored deubiquitinase that governs organelle quality control by opposing ubiquitin-dependent degradation of mitochondria and peroxisomes. It preferentially cleaves Lys6-linked ubiquitin chains and removes ubiquitin from key mitochondrial substrates—including TOM20, TOM40, MFN1/2, and HK1/2—thereby setting the activation threshold for PINK1/Parkin-amplified mitochondrial ubiquitylation and mitophagy; its activity is itself attenuated by PINK1-generated phospho-Ser65 ubiquitin and stabilized by CDK5-mediated phosphorylation at Ser216 (PMID:24896179, PMID:28945249, PMID:32142685, PMID:38772138). Beyond mitophagy, USP30 localizes to peroxisomes where it counteracts the E3 ligase PEX2 to suppress pexophagy, regulates BAX/BAK-dependent apoptosis, and deubiquitinates cytosolic substrates including Snail, FTO, and C/EBPβ to influence epithelial–mesenchymal transition, serine metabolism, and lipid accumulation (PMID:30700497, PMID:25739811, PMID:38146008, PMID:41652187, PMID:39433172). Genetic ablation of USP30 in mice protects dopaminergic neurons against α-synuclein-induced neurodegeneration by enhancing mitophagy, establishing USP30 as a therapeutic target in Parkinson's disease (PMID:37957154).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2008 High

    The identity of USP30 as a mitochondrial outer membrane deubiquitinase with a role in mitochondrial morphology was unknown; RNAi depletion produced elongated, interconnected mitochondria rescued only by catalytically active USP30, establishing it as a DUB that controls mitochondrial dynamics through deubiquitination.

    Evidence RNAi knockdown with catalytic-mutant rescue and live-cell imaging in mammalian cells

    PMID:18287522

    Open questions at the time
    • Specific substrates controlling morphology not identified
    • Mechanism linking deubiquitination to mitofusin-dependent elongation unclear
  2. 2014 High

    Whether mitophagy was directly opposed by a specific DUB was unresolved; global ubiquitin-site profiling and Drosophila genetics demonstrated that USP30 removes ubiquitin from Parkin substrates on damaged mitochondria, blocking mitophagy, and that its knockdown rescues parkin/PINK1 loss-of-function phenotypes in vivo.

    Evidence Overexpression/RNAi, ubiquitination-site mass spectrometry, mitophagy assays, Drosophila dopaminergic neuron rescue

    PMID:24896179

    Open questions at the time
    • Precise chain-linkage specificity not yet determined
    • Endogenous substrate hierarchy on mitochondria unknown
  3. 2015 High

    The specific outer membrane target of USP30 opposition to Parkin was clarified: USP30 deubiquitinates TOM20 and modulates BAX/BAK-dependent apoptosis, linking USP30 to both mitophagy and cell death pathways.

    Evidence Co-IP of TOM20 ubiquitylation, apoptosis assays with BH3-mimetics upon USP30 depletion

    PMID:25739811

    Open questions at the time
    • Whether TOM20 is the primary or only critical substrate was not established
    • Structural basis for substrate recognition unknown
  4. 2017 High

    The structural and biochemical basis for USP30's unusual Lys6-linkage preference was resolved: crystal structures of USP30 with mono- and diubiquitin revealed unique binding interfaces, and PINK1-generated phospho-Ser65 ubiquitin was shown to inhibit USP30 activity, establishing a reciprocal regulatory circuit.

    Evidence X-ray crystallography, in vitro chain cleavage assays, mutagenesis, biochemical reconstitution

    PMID:28945249

    Open questions at the time
    • Full-length USP30 structure including TM domain not resolved
    • In vivo significance of Lys6 selectivity versus other linkages on mitochondria not quantified
  5. 2018 High

    USP30 function was extended beyond mitophagy to peroxisome turnover: endogenous USP30 was shown to localize to peroxisomes and regulate basal pexophagy independently of PINK1/Parkin, and separately, GNPAT was found to recruit USP30 to deubiquitinate and stabilize DRP1 for mitochondrial fission.

    Evidence Subcellular fractionation, pexophagy/mitophagy reporters, co-IP of USP30–DRP1 interaction

    PMID:29895712 PMID:30143522

    Open questions at the time
    • Peroxisomal targeting mechanism of USP30 not determined
    • Whether DRP1 stabilization involves Lys6 chains not tested
  6. 2019 High

    The peroxisomal E3 ligase counteracted by USP30 was identified as PEX2, establishing a DUB–E3 antagonism that controls pexophagy during amino acid starvation.

    Evidence Live-cell imaging, genetic epistasis with PEX2, pexophagy flux assays

    PMID:30700497

    Open questions at the time
    • Identity of peroxisomal substrates deubiquitinated by USP30 not fully characterized
    • Regulation of USP30 partitioning between mitochondria and peroxisomes unknown
  7. 2020 High

    Quantitative ubiquitylomics in endogenous-expression iNeurons showed that USP30 primarily targets TOM complex components and sets a trigger threshold for PINK1/Parkin ubiquitin amplification, and TOM20 ubiquitylation was validated as a robust biomarker of USP30 loss or inhibition.

    Evidence CRISPR KO iNeurons, quantitative proteomics/ubiquitylomics, parallel chemical inhibition with FT3967385

    PMID:32142685 PMID:32636217

    Open questions at the time
    • Whether translocon-clogging substrates are direct USP30 targets or indirect effects not resolved
    • Long-term consequences of chronic USP30 loss in neurons not assessed
  8. 2021 Medium

    USP30 was linked to additional non-mitochondrial functions: deubiquitination of NLRP3 inflammasome components, deubiquitination of Bax regulating apoptosis, and CDK5-mediated Ser216 phosphorylation was identified as a stabilizing post-translational modification coupling kinase signaling to USP30 protein levels.

    Evidence Co-IP, ubiquitination assays, pharmacological inhibition (MF-094, aumdubin), phosphorylation mapping, MPTP PD model

    PMID:34381024 PMID:34883112 PMID:38772138

    Open questions at the time
    • NLRP3 and Bax interactions each from single labs without independent replication
    • Whether CDK5 phosphorylation affects catalytic activity or only stability not distinguished
  9. 2023 High

    In vivo therapeutic relevance was demonstrated: USP30 knockout in mice protected dopaminergic neurons against α-synuclein-induced neurodegeneration by enhancing mitophagy, and a brain-penetrant inhibitor MTX115325 recapitulated the protection, validating USP30 as a Parkinson's disease target.

    Evidence Usp30 KO mice, α-synuclein overexpression PD model, pharmacological inhibition, behavioral and histological readouts

    PMID:37957154

    Open questions at the time
    • Long-term safety of chronic USP30 inhibition in aging brain not established
    • Contribution of pexophagy versus mitophagy to neuroprotection not dissected
  10. 2025 High

    The structural basis for selective pharmacological inhibition was resolved: a crystal structure revealed that a specific inhibitor binds a cryptic pocket formed by a compound-induced conformation of the USP30 switching loop, with a ligandability hotspot at the Leu73 ubiquitin-binding site.

    Evidence X-ray crystallography of chimeric USP30–inhibitor complex, SAR analysis, enzymatic assays

    PMID:40325251

    Open questions at the time
    • Whether the cryptic pocket is exploitable for all chemotypes not known
    • Full-length membrane-anchored USP30 structure still not available
  11. 2025 Medium

    USP30's role was expanded to T cell biology: prolonged TCR/NFAT1 signaling transcriptionally upregulates USP30 in exhausted CD8+ T cells, and USP30 deletion or inhibition restores mitophagy and antitumor effector function.

    Evidence Genetic deletion, pharmacological inhibition, TCR/NFAT1 pathway analysis, in vivo tumor models

    PMID:40815646

    Open questions at the time
    • Single-lab finding not yet independently replicated
    • Whether USP30-driven T cell exhaustion operates through the same substrates (TOM complex) as in neurons is unknown
  12. 2026 Medium

    USP30's substrate repertoire was further expanded to include metabolic regulators: USP30 deubiquitinates and stabilizes FTO to promote serine synthesis via m6A-dependent mRNA regulation, and deubiquitinates HK1/HK2 at specific sites (K144 of HK2) to enhance glycolysis and mitochondrial hexokinase activity.

    Evidence Co-IP, ubiquitination assays, m6A profiling, ubiquitinomics, site-directed mutagenesis, in vivo tumor models

    PMID:41652187 PMID:41688443

    Open questions at the time
    • FTO and HK1/2 interactions each from single labs
    • Whether these substrates are deubiquitinated at mitochondria or in the cytosol not resolved
    • Chain-linkage specificity for HK1/2 described as atypical but not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for USP30's dual mitochondrial/peroxisomal targeting, the full substrate hierarchy under physiological conditions, whether chronic USP30 inhibition has deleterious effects on organelle homeostasis in aging tissues, and the relative contribution of Lys6- versus K48-linked chain cleavage to its diverse biological functions.
  • No full-length structure including TM domain
  • Substrate prioritization under endogenous conditions in non-neuronal tissues poorly defined
  • Long-term in vivo safety of USP30 inhibition not systematically assessed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 12 GO:0140096 catalytic activity, acting on a protein 8
Localization
GO:0005739 mitochondrion 7 GO:0005777 peroxisome 2
Pathway
R-HSA-9612973 Autophagy 7 R-HSA-392499 Metabolism of proteins 6 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-5357801 Programmed Cell Death 3
Partners
DRP1FTOHK2MFN2PEX2PINK1TOM20TOMM40

Evidence

Reading pass · 31 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; its depletion by RNAi induces elongated, interconnected mitochondria dependent on mitofusin activity, and this phenotype is rescued by catalytically active USP30, establishing USP30 as a regulator of mitochondrial morphology via deubiquitination. RNAi knockdown, ectopic re-expression with catalytic mutants, live-cell imaging of mitochondrial morphology, fractionation to mitochondrial outer membrane Molecular biology of the cell High 18287522
2014 USP30 opposes PINK1/Parkin-mediated mitophagy by removing ubiquitin from Parkin substrates on damaged mitochondria; overexpression of USP30 blocks mitophagy, while USP30 knockdown enhances mitochondrial degradation. Global ubiquitination-site profiling identified multiple mitochondrial substrates oppositely regulated by Parkin and USP30. Knockdown of USP30 in Drosophila dopaminergic neurons rescues defects caused by parkin/PINK1 loss. Overexpression and RNAi knockdown, ubiquitination site profiling by mass spectrometry, mitophagy assays, Drosophila genetic rescue Nature High 24896179
2014 USP30 is a target of the mitochondrial fusion-inducing compound 15-oxospiramilactone (S3); its inhibition leads to non-degradative ubiquitination of Mfn1/2, which enhances mitofusin activity and promotes mitochondrial fusion, revealing a role for USP30 in regulating Mfn1/2 ubiquitination status. Chemical inhibition with S3, ubiquitination assays of Mfn1/2, mitochondrial morphology imaging, target identification Cell research Medium 24513856
2015 USP30 opposes Parkin-dependent ubiquitylation of TOM20 on mitochondria; its depletion enhances depolarization-induced apoptotic cell death in Parkin-overexpressing cells and also sensitizes cancer cells to BH3-mimetics by regulating BAX/BAK-dependent apoptosis. USP30 depletion/overexpression, co-IP of TOM20 ubiquitylation, apoptosis assays with BH3-mimetics EMBO reports High 25739811
2017 Crystal structures of human USP30 bound to monoubiquitin and Lys6-linked diubiquitin reveal unique ubiquitin-binding interfaces that explain USP30's Lys6-linkage preference. Distally phosphorylated ubiquitin chains (pSer65-Ub) impair USP30 activity. USP30 regulates Lys6-polyubiquitinated TOM20. Active-site architecture and regulation by PINK1-phospho-ubiquitin were established. X-ray crystallography, in vitro ubiquitin chain cleavage assays, linkage-specific affimers, mutagenesis, biochemical reconstitution Nature structural & molecular biology High 28945249
2018 GNPAT recruits USP30 to deubiquitylate and stabilize DRP1, thereby facilitating mitochondrial fission and lipid metabolism in hepatocellular carcinoma; USP30 interaction with DRP1 was demonstrated by co-IP. Co-immunoprecipitation, ubiquitination assays, knockdown/overexpression, mitochondrial morphology analysis Cancer research Medium 30143522
2018 USP30 acts upstream of PINK1 to regulate basal mitophagy in Parkin-null cells by modulating PINK1-substrate availability; additionally, a fraction of endogenous USP30 localizes to peroxisomes where it regulates basal pexophagy in a PINK1- and Parkin-independent manner. Mitophagy reporter assays, USP30 depletion, subcellular fractionation/immunofluorescence for peroxisomal localization, pexophagy reporters EMBO reports High 29895712
2019 USP30 localizes to peroxisomes and counteracts the peroxisomal E3 ubiquitin ligase PEX2 to prevent pexophagy; overexpression of USP30 blocks amino acid starvation-induced pexophagy and its depletion induces basal pexophagy. Live-cell imaging, subcellular fractionation, overexpression and knockdown of USP30, pexophagy flux assays, genetic interaction with PEX2 The Journal of cell biology High 30700497
2020 In induced neurons (iNeurons) under endogenous expression conditions, USP30 loss preferentially affects ubiquitylation of mitochondrial translocon (TOM complex) components; USP30 sets a trigger threshold for PINK1-Parkin amplification of mitochondrial ubiquitylation and also has a basal quality-control function on ubiquitylated translocon import substrates. Quantitative proteomics/ubiquitylomics in USP30−/− iNeurons, mitophagy flux assays, CRISPR knockout Molecular cell High 32142685
2020 USP30 deubiquitylation of TOM complex components (including TOM20) dampens the trigger for Parkin-dependent amplification of mitochondrial ubiquitylation leading to mitophagy; TOM20 ubiquitylation is a robust biomarker for USP30 loss or inhibition, and pSer65-Ub proceeds more rapidly in USP30-inhibited cells. Proteomics comparing USP30 KO vs. chemical inhibition (FT3967385), ubiquitylation profiling in neuroblastoma cells, biochemical assays Life science alliance High 32636217
2020 Noncanonical tryptophan analogues incorporated at W475 in USP30 alter its activity and diubiquitin linkage selectivity; the formyl-indole analogue at W475 enhances polar interactions and USP30 activity, while 3-benzothienyl-l-alanine induces unique K6-specificity, demonstrating the role of W475 in diubiquitin selectivity at the active site. Genetic code expansion with evolved PylRS, noncanonical amino acid incorporation, in vitro ubiquitin cleavage assays, X-ray crystallography of PylRS-analogue complexes Biochemistry Medium 32484330
2021 USP30 deubiquitylates NLRP3 inflammasome components, activating the NLRP3 inflammasome; this interaction was demonstrated by co-immunoprecipitation and ubiquitination assays, and USP30 inhibition (MF-094) reduced NLRP3 and caspase-1 activation in diabetic wound models. Co-immunoprecipitation, ubiquitination assays, shRNA knockdown, USP30 inhibitor MF-094 in vitro and in vivo Experimental cell research Medium 34883112
2021 USP30 inhibition in a SAH model promotes ubiquitination of MFN2 by Parkin, separating damaged mitochondria from the healthy network and promoting mitophagy; USP30 opposes MFN2 ubiquitination and thereby inhibits mitophagy. In vitro (hemoglobin exposure model) and in vivo (intravascular perforation) SAH models, ubiquitination assays of MFN2, USP30 inhibitor MF094 Translational stroke research Medium 38147294
2021 USP30 overexpression suppresses mitochondrial fragmentation and degradation of MFN2 under oxygen-glucose deprivation/reperfusion injury by preventing ubiquitination of MFN2; overexpression of MFN2 itself attenuates mitochondrial fragmentation. OGD/reperfusion cell model, USP30 overexpression, ubiquitination assays of MFN2, mitochondrial morphology analysis Aging Medium 33609088
2021 USP30 promotes Bax-dependent apoptosis by deubiquitinating and reducing mitochondrial accumulation of Bax; the gold compound aumdubin shows high affinity for USP30 and induces apoptosis by increasing Bax ubiquitination and mitochondrial localization through USP30 inhibition. Affinity binding assays, ubiquitination assays of Bax, apoptosis assays, USP30 inhibition by aumdubin Cell death discovery Medium 34381024
2022 A peptide (Q14) derived from the transmembrane domain of USP30 inhibits USP30 through a novel autoinhibitory mechanism by binding to potential allosteric sites on USP30 and separately promotes autophagosome formation via its LC3-interacting region (LIR) motif. Fluorescence polarization, microscale thermophoresis, in vitro USP30 activity assays (Ub-AMC), autophagy reporter assays, LC3 binding assay Autophagy Medium 34989313
2022 USP30 regulates AKT/mTOR signaling downstream of mitochondrial stress: Parkin inhibits AKT/mTOR to promote apoptosis following mitochondrial stress, while USP30 overexpression antagonizes Parkin activity to sustain AKT/mTOR signaling and inhibit apoptosis. Genetic overexpression/knockdown of Parkin and USP30, AKT/mTOR pathway phosphorylation assays, apoptosis assays under mitochondrial stress Frontiers in pharmacology Medium 35250566
2023 USP30 interacts with and stabilizes Snail protein through deubiquitination, specifically removing K48-linked polyubiquitin chains, thereby promoting Snail-driven EMT in breast cancer cells. Co-immunoprecipitation, ubiquitination assays (K48-linkage specific), knockdown/overexpression, EMT and invasion assays Cancer gene therapy Medium 38146008
2023 USP30 knockout in mice protects dopaminergic neurons against α-synuclein-induced neurodegeneration; loss of USP30 increases mitophagy and decreases phospho-S129 α-synuclein and SN dopaminergic neuronal loss, recapitulated by a brain-penetrant USP30 inhibitor MTX115325. Usp30 knockout mice, α-synuclein overexpression PD model, behavioral assays, immunohistochemistry, pharmacological inhibition with MTX115325 Nature communications High 37957154
2023 CDK5 phosphorylates USP30 at serine 216 to stabilize USP30 protein; stabilized USP30 then suppresses mitophagy and activates MAVS-mediated neuroinflammation in an MPTP/MPP+ PD model. CDK5 inhibition reduces USP30 levels and suppresses MAVS pathway activation. CDK5 inhibition, phosphorylation assays, USP30 knockdown, mitophagy assays, MAVS inflammation pathway analysis in microglial cells and in vivo MPTP model Ecotoxicology and environmental safety Medium 38772138
2024 NPRC recruits USP30 to deubiquitinate C/EBPβ at K149 via K48-linked polyubiquitin removal; the DNA-binding domain of C/EBPβ interacts with USP30, and NPRC's ANPR region binds USP30 to facilitate this deubiquitination, stabilizing C/EBPβ and promoting lipid accumulation. Proteomic analysis, ubiquitination assays (K149 site-specific), co-immunoprecipitation, domain mapping Metabolism: clinical and experimental Medium 39433172
2024 USP30 deubiquitinates TOMM40 to reduce its ubiquitination level and stabilize it; USP30 binds TOMM40 (demonstrated by co-IP) and promotes breast cancer cell proliferation and tamoxifen resistance through this mechanism. Co-immunoprecipitation, ubiquitination assays, knockdown/overexpression, tamoxifen resistance assays Journal of biochemical and molecular toxicology Medium 40227042
2024 FOXF1 induces HMGA2 transcription, and HMGA2 recruits USP30 (demonstrated by co-IP and mass spectrometry) to deubiquitinate and stabilize S100A6, promoting ovarian cancer metastasis. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, luciferase assays, functional rescue experiments Biochimica et biophysica acta. Molecular basis of disease Medium 39694080
2025 Crystal structure of human USP30 in complex with a specific small-molecule inhibitor (enabled by chimeric protein engineering) reveals that the inhibitor binds a cryptic pocket formed by a compound-induced conformation of the USP30 switching loop; a common ligandability hotspot at the Leu73 ubiquitin-binding site underlies specific USP30 inhibition. X-ray crystallography of chimeric USP30-inhibitor complex, structure-activity relationship analysis, enzymatic assays Nature structural & molecular biology High 40325251
2025 USP30 depletion stabilizes and reduces MAT2A protein through a deubiquitination-dependent mechanism, lowering SAM levels (~40%), reducing global DNA methylation (~35%), and upregulating miR-30a-5p, which suppresses MDM2 and NFAT5 to maintain endothelial cell function; this is a mitophagy-independent role for USP30. EC-specific USP30 knockout mice, lung injury models, proteomics, methylation assays, miRNA profiling, biochemical ubiquitination assays Advanced science Medium 41104980
2025 Prolonged antigen stimulation drives TCR/NFAT1 signaling to transcriptionally upregulate USP30 in exhausted CD8+ T cells; USP30 genetic deletion or pharmacological inhibition restores mitophagy, improves mitochondrial fitness, and rejuvenates CD8+ T cell effector functions and antitumor responses. Genetic deletion and pharmacological inhibition of USP30, TCR/NFAT1 pathway analysis, mitophagy flux assays, T cell functional assays, in vivo tumor models Science advances Medium 40815646
2026 USP30 binds serine/glycine and senses their levels; it protects FTO from proteasomal degradation through deubiquitination. Stabilized FTO demethylates PHGDH and PSAT1 mRNAs in an m6A-YTHDF2-dependent manner, promoting serine synthesis and colorectal cancer growth. Co-immunoprecipitation, ubiquitination assays, m6A profiling, metabolomics, genetic knockdown/overexpression, in vivo tumor models Cell death and differentiation Medium 41652187
2026 USP30 interacts with and deubiquitinates HK1 and HK2 by removing atypical ubiquitin chains, enhancing their stability, mitochondrial localization, VDAC1 binding, and hexokinase activity; K144 of HK2 is a critical regulatory site for USP30-mediated deubiquitination, and its mutation enhances glycolysis and tumor growth. Quantitative proteomics, ubiquitinomics, co-immunoprecipitation, site-directed mutagenesis (K144), in vitro hexokinase activity assays, in vivo tumor models Cell death & disease Medium 41688443
2026 USP30 overexpression stabilizes MFN2 through deubiquitination, reducing ubiquitination of MFN2 and protecting mitochondria-associated ER membranes (MAMs); knockdown of MFN2 abrogates the protective effect of USP30 on MAMs in intestinal ischemia-reperfusion injury. Overexpression and knockdown of USP30 and MFN2, ubiquitination assays, electron microscopy, MAM analysis, intestinal I/R model Biochemical pharmacology Medium 41765114
2025 USP30 loss or inhibition alters mitochondrial morphology and increases mitochondrial membrane potential and ATP levels with decreased oxygen consumption in a PINK1/Parkin-independent manner; chronic USP30 inhibition does not impair dopaminergic neuronal activity in iPSC-derived neurons. CRISPRn KO, CRISPRi knockdown, pharmacological inhibition, mitochondrial morphology imaging, electrophysiology in iPSC-derived dopaminergic neurons, mitophagy reporters bioRxivpreprint Medium bio_10.1101_2025.02.03.636341
2024 LETM1 was identified as a novel USP30 substrate using proximity-labeling (APEX2) combined with ubiquitination enrichment (K-ε-GG); previously described USP30 substrates TOMM20 and FKBP8 were also confirmed in the proximity-ubiquitome upon USP30 inhibition. APEX2 proximity labeling, diGly ubiquitinomics by mass spectrometry, USP30 inhibition bioRxivpreprint Low bio_10.1101_2024.10.07.616967

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 679 24896179
2016 Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond. Free radical biology & medicine 261 27094585
2014 A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30. Cell research 178 24513856
2017 Mechanism and regulation of the Lys6-selective deubiquitinase USP30. Nature structural & molecular biology 175 28945249
2020 Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling. Molecular cell 161 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 139 25739811
2018 Dual role of USP30 in controlling basal pexophagy and mitophagy. EMBO reports 129 29895712
2018 Novel highly selective inhibitors of ubiquitin specific protease 30 (USP30) accelerate mitophagy. Bioorganic & medicinal chemistry letters 100 29935771
2020 USP30 sets a trigger threshold for PINK1-PARKIN amplification of mitochondrial ubiquitylation. Life science alliance 98 32636217
2023 Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model. Nature communications 64 37957154
2019 Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy. The Journal of cell biology 57 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 46 34844982
2021 Investigation of USP30 inhibition to enhance Parkin-mediated mitophagy: tools and approaches. The Biochemical journal 44 34704599
2022 USP30: Structure, Emerging Physiological Role, and Target Inhibition. Frontiers in pharmacology 42 35308234
2022 Identification of an autoinhibitory, mitophagy-inducing peptide derived from the transmembrane domain of USP30. Autophagy 40 34989313
2021 Pharmacological inhibition of USP30 activates tissue-specific mitophagy. Acta physiologica (Oxford, England) 38 33890401
2024 USP30 inhibition induces mitophagy and reduces oxidative stress in parkin-deficient human neurons. Cell death & disease 36 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 31 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
2021 USP30-AS1 contributes to mitochondrial quality control in glioblastoma cells. Biochemical and biophysical research communications 25 34653676
2023 Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule Benzosulfonamides. Molecular & cellular proteomics : MCP 24 37385347
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
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
2021 Regulation of Bax-dependent apoptosis by mitochondrial deubiquitinase USP30. Cell death discovery 16 34381024
2023 USP30 promotes the progression of breast cancer by stabilising Snail. Cancer gene therapy 14 38146008
2022 The Mitochondrial Deubiquitinase USP30 Regulates AKT/mTOR Signaling. Frontiers in pharmacology 14 35250566
2023 Chaihu Shugan Powder inhibits interstitial cells of cajal mitophagy through USP30 in the treatment of functional dyspepsia. Journal of ethnopharmacology 13 38163556
2025 Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30. Nature structural & molecular biology 11 40325251
2019 New aspects of USP30 biology in the regulation of pexophagy. Autophagy 11 31356149
2025 An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection. PLoS pathogens 10 39777915
2024 Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30. RSC chemical biology 8 38725909
2018 Organelle Turnover: A USP30 Safety Catch Restrains the Trigger for Mitophagy and Pexophagy. Current biology : CB 8 30086320
2024 CDK5-USP30 signaling pathway regulates MAVS-mediated inflammation via suppressing mitophagy in MPTP/MPP+ PD model. Ecotoxicology and environmental safety 7 38772138
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 USP30 inhibition augments mitophagy to prevent T cell exhaustion. Science advances 5 40815646
2024 NPRC promotes hepatic steatosis via USP30-mediated deubiquitination of C/EBPβ. Metabolism: clinical and experimental 5 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
2025 Long noncoding RNA USP30-AS1 promotes influenza A virus replication by enhancing PHB1 function. Veterinary microbiology 4 40020267
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
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
2024 Modulation of OPC Mitochondrial Function by Inhibiting USP30 Promotes Their Differentiation. Glia 3 39601128
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 Spotlight on USP30: structure, function, disease and target inhibition. Frontiers in pharmacology 2 40918504
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 Activation of USP30 Disrupts Endothelial Cell Function and Aggravates Acute Lung Injury Through Regulating the S-Adenosylmethionine Cycle. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41104980
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 Knockdown Drives Mitophagy and Suppresses Pyroptosis in Heart Failure by Activating the PINK1/Parkin Pathway. International heart journal 0 41320325
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