Affinage

MUL1

Mitochondrial ubiquitin ligase activator of NFKB 1 · UniProt Q969V5

Length
352 aa
Mass
39.8 kDa
Annotated
2026-04-29
63 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUL1 is a mitochondrial outer membrane-anchored dual E3 ligase that uses its cytosol-facing RING finger domain to catalyze both ubiquitination and SUMOylation of diverse substrates, thereby coordinating mitochondrial dynamics, mitophagy, apoptosis, innate immune signaling, and cellular metabolism. As a ubiquitin E3 ligase, MUL1 K48-polyubiquitinates Mitofusin 1/2, Akt, ULK1, UBXN7, HSPA5, and HIF-1α for proteasomal degradation, functioning in parallel with the PINK1/Parkin pathway to maintain mitochondrial integrity and regulate the balance between oxidative phosphorylation and glycolysis (PMID:24898855, PMID:22410793, PMID:32005965, PMID:35846359). As a SUMO E3 ligase, MUL1 SUMOylates DRP1 to promote mitochondrial fission and stabilize ER–mitochondria contact sites during apoptosis, SUMOylates RIG-I to enable antiviral innate immune activation, and SUMOylates NDP52 and ABCD3 to regulate mitophagy and peroxisomal bile acid transport, respectively (PMID:19407830, PMID:26384664, PMID:28273895, PMID:37942585, PMID:37962001). MUL1 also drives pyroptosis through a pathway in which mitochondrial DNA is trafficked via mitochondrial-derived vesicles to lysosomes, permeabilized through gasdermin pores, and released into the cytosol to activate cGAS (PMID:41083601).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2008 High

    The identity of MUL1 as a mitochondrial outer membrane E3 ubiquitin ligase was established, resolving how a RING-domain protein anchored to mitochondria could influence both mitochondrial dynamics and NF-κB signaling.

    Evidence Ectopic expression, RNAi, domain mutagenesis, and subcellular fractionation in mammalian cells

    PMID:18213395 PMID:18591963

    Open questions at the time
    • The endogenous substrates for MUL1 ubiquitin ligase activity were not identified
    • Mechanism linking MUL1 to NF-κB remained indirect
    • Whether MUL1 had ligase activities beyond ubiquitination was unknown
  2. 2009 High

    Discovery that MUL1 functions as the first mitochondria-anchored SUMO E3 ligase — SUMOylating DRP1 to stimulate fission — established its dual enzymatic identity and explained how mitochondrial fission is locally regulated.

    Evidence In vitro SUMOylation assays, RNAi, and co-immunoprecipitation

    PMID:19407830

    Open questions at the time
    • How SUMOylation of DRP1 mechanistically promotes its mitochondrial recruitment was unclear
    • Whether SUMO1 vs SUMO2/3 specificity matters was not resolved
  3. 2012 High

    Identification of Akt as a direct ubiquitination substrate revealed MUL1's reach beyond mitochondrial dynamics into growth-factor signaling and cell survival pathways.

    Evidence In vitro and in vivo ubiquitination assays, reciprocal Co-IP, cell proliferation assays

    PMID:22410793

    Open questions at the time
    • Which Akt isoform is preferentially targeted was not distinguished
    • Physiological context in which MUL1-Akt regulation is dominant was unknown
  4. 2014 High

    Genetic epistasis across Drosophila and mammals demonstrated that MUL1 ubiquitinates Mitofusin for proteasomal degradation in a pathway parallel to PINK1/Parkin, establishing functional redundancy in mitochondrial quality control.

    Evidence Drosophila double-mutant genetics, mouse cortical neuron assays, ubiquitination assays

    PMID:24898855

    Open questions at the time
    • Whether MUL1 preferentially targets Mfn1 vs Mfn2 in different tissues was unresolved
    • Upstream signals activating MUL1 in the PINK1/Parkin-parallel pathway were unknown
  5. 2014 Medium

    Identification of MUL1's E2 partners (Ube2E2, Ube2E3, Ube2G2, Ube2L3) and an LIR motif in the RING domain linking MUL1-Ube2E3 to GABARAP provided the first molecular framework for how MUL1 connects ubiquitination to autophagy receptor engagement.

    Evidence Modified yeast two-hybrid, Co-IP, LIR mutagenesis

    PMID:25224329

    Open questions at the time
    • LIR-GABARAP interaction not validated by structural methods
    • Functional contribution of each E2 to distinct substrate ubiquitination not determined
    • Omi/HtrA2 proteolytic regulation of MUL1 turnover identified in parallel but upstream triggers remain unclear
  6. 2015 High

    During apoptosis, MUL1-dependent DRP1 SUMOylation was shown to stabilize ER–mitochondria contact sites required for mitochondrial constriction, calcium flux, and cytochrome c release downstream of BAX/BAK, positioning MUL1 as an effector of the intrinsic apoptotic program.

    Evidence MAPL KO/KD, live ER-mitochondria imaging, SUMOylation and cytochrome c release assays

    PMID:26384664

    Open questions at the time
    • How BAX/BAK activation signals to MUL1 was not elucidated
    • Whether MUL1 SUMOylation of DRP1 at ER-mitochondria contacts differs from bulk DRP1 SUMOylation was unknown
  7. 2016 High

    MUL1 and Parkin were shown to act redundantly in eliminating paternal mitochondria via mitophagy in mouse embryos, demonstrating a physiological requirement for MUL1 in uniparental mitochondrial inheritance.

    Evidence Double genetic KO of MUL1 and Parkin in mouse embryos, mitophagy flux assays

    PMID:27852436

    Open questions at the time
    • Specific ubiquitination substrates mediating paternal mitophagy were not identified
    • Whether MUL1's SUMO ligase activity also contributes was untested
  8. 2017 High

    MUL1 was established as the SUMO E3 ligase for RIG-I, with SUMOylation shown to be a prerequisite for RIG-I activation and antiviral transcription; this resolved earlier observations linking MUL1 to innate immune signaling.

    Evidence MAPL KO in vivo and in vitro, BioID proximity labeling, constitutively active RIG-I epistasis

    PMID:28273895

    Open questions at the time
    • Which SUMOylation sites on RIG-I are modified by MUL1 was not mapped
    • How MUL1 is recruited to RIG-I upon viral infection was unclear
  9. 2019 High

    Structural analysis of the MUL1 RING domain revealed a ββαβ fold with canonical cross-brace zinc coordination and direct binding to p53 transactivation domain, providing the first atomic-resolution view of substrate recognition by this ligase.

    Evidence NMR solution structure and chemical shift perturbation mapping

    PMID:31235254 PMID:35048531

    Open questions at the time
    • Full-length MUL1 structure including transmembrane anchors remains undetermined
    • Whether p53 ubiquitination by MUL1 is physiologically significant in vivo is unknown
  10. 2019 High

    MUL1 KO in neurons demonstrated that MUL1 antagonizes Mfn2-mediated ER-mitochondria tethering; loss of MUL1 elevates Mfn2, disrupts ER-mitochondria calcium coupling, and paradoxically triggers calcineurin-dependent DRP1 activation and Parkin-mediated mitophagy.

    Evidence MUL1 KO neurons, live imaging of ER-mitochondria contacts, calcium measurements, Mfn2 overexpression phenocopy, calcineurin inhibition

    PMID:31409786

    Open questions at the time
    • Whether this feedback loop operates in non-neuronal cells was not tested
    • Direct calcineurin-DRP1 dephosphorylation in this context was not biochemically reconstituted
  11. 2020 Medium

    Identification of UBXN7 and Akt2/HIF-1α as MUL1 ubiquitination substrates established that MUL1 regulates the metabolic switch between oxidative phosphorylation and glycolysis by controlling HIF-1α stability through multiple converging mechanisms.

    Evidence MUL1 KO cells, metabolic flux analysis, ubiquitination assays, metabolomics/lipidomics

    PMID:32005965 PMID:35846359

    Open questions at the time
    • Whether MUL1 directly ubiquitinates HIF-1α or only indirectly controls it via UBXN7/Akt2 was not fully resolved
    • Tissue-specific metabolic consequences in vivo not characterized
  12. 2023 Medium

    Expansion of MUL1's SUMO substrate repertoire to include NDP52 (mitophagy receptor) and ABCD3 (peroxisomal transporter) showed that MUL1 SUMOylation regulates organelle-specific processes beyond mitochondria, including peroxisomal bile acid metabolism and endosome-mediated mitophagy.

    Evidence SUMOylation proteomics, site-specific mutagenesis (NDP52 K262R), BioID, MAPL KO mice with metabolic profiling

    PMID:37942585 PMID:37962001

    Open questions at the time
    • How MUL1 on the mitochondrial outer membrane accesses peroxisomal ABCD3 is mechanistically unclear
    • Whether NDP52 SUMOylation is required for mitophagy in vivo has not been tested
  13. 2025 High

    A genome-wide CRISPR screen revealed that MUL1 induces pyroptosis by directing mitochondrial DNA through mitochondrial-derived vesicles to lysosomes, which are permeabilized by gasdermin pores to release mtDNA into the cytosol for cGAS activation — linking MUL1 to Parkinson's disease genes VPS35 and LRRK2.

    Evidence Genome-wide CRISPR screen, mtDNA trafficking assays, gasdermin pore assays, cGAS activation, primary macrophage experiments

    PMID:41083601

    Open questions at the time
    • The direct MUL1 substrate(s) initiating mitochondrial-derived vesicle formation for this pathway are unknown
    • Whether MUL1-driven pyroptosis contributes to neurodegeneration in Parkinson's disease models has not been tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structural model of MUL1 including its transmembrane domains and the basis for substrate selectivity between ubiquitination and SUMOylation remain unresolved; how upstream signals dynamically regulate MUL1 activity and its partitioning between dual ligase functions is unknown.
  • No full-length structure of MUL1 including transmembrane domains exists
  • Mechanism by which MUL1 switches between ubiquitin and SUMO E3 ligase activities is unknown
  • Upstream regulatory signals controlling MUL1 enzymatic activity under physiological conditions are largely uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 13 GO:0016874 ligase activity 5
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-9612973 Autophagy 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2
Partners
ABCD3AKT1DRP1MFN2NDP52RIG-ITRAF2UBXN7

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MULAN/MUL1 is a mitochondrial outer membrane protein with two transmembrane domains mediating localization and a C-terminal RING finger domain exposed to the cytosol that confers E3 ubiquitin ligase activity; both intact RING finger and correct subcellular localization are required for regulation of mitochondrial dynamics and NF-κB activation. Ectopic expression and RNAi knockdown with imaging, domain mutagenesis, subcellular fractionation PloS one High 18213395
2009 MAPL/MUL1 functions as the first mitochondria-anchored SUMO E3 ligase; it SUMOylates DRP1 to stimulate mitochondrial fission. Biochemical SUMOylation assays, overexpression and RNAi knockdown, co-immunoprecipitation EMBO reports High 19407830
2008 GIDE/MUL1 induces apoptosis via caspase activation and JNK-dependent cytochrome c and Smac release; the pro-apoptotic activity requires its E3 ubiquitin ligase (RING finger) activity. Overexpression, caspase inhibitor treatment, dominant-negative caspase-9, JNK inhibition, RING finger mutagenesis Cell research High 18591963
2014 MUL1 acts in parallel to the PINK1/parkin pathway by ubiquitinating Mitofusin (Mfn) to target it for proteasomal degradation, thereby maintaining mitochondrial integrity; MUL1 suppresses PINK1 or parkin mutant phenotypes in Drosophila and compensates for their loss in mammals. Drosophila genetic epistasis, loss-of-function double mutants, mouse cortical neuron degeneration assay, ubiquitination assay eLife High 24898855
2015 During apoptosis, MAPL/MUL1-dependent SUMOylation of Drp1 stabilizes ER/mitochondrial contact sites required for mitochondrial constriction, calcium flux, cristae remodeling, and cytochrome c release; MAPL acts downstream of BAX/BAK activation. MAPL knockout/knockdown, SUMOylation assay, live imaging of ER-mitochondria contacts, cytochrome c release assay, BAX/BAK oligomer analysis Molecular cell High 26384664
2012 MULAN/MUL1 negatively regulates Akt by directly interacting with and ubiquitinating phosphorylated Akt, leading to its proteasomal degradation and suppression of cell proliferation and viability. Co-immunoprecipitation, in vitro ubiquitination assay, in vivo ubiquitination assay, cell proliferation/viability assays Cell research High 22410793
2016 MUL1 and PARKIN play redundant roles in elimination of paternal mitochondria via mitophagy in mouse embryos; the process requires mitochondrial depolarization, FIS1, P62, and PINK1 kinase. Mouse embryo mitophagy assay, autophagosome/lysosome tracking, genetic knockouts of PARKIN and MUL1, pre-implantation embryo culture eLife High 27852436
2015 MUL1 ubiquitinates ULK1 (a key autophagy kinase) which partially translocates to mitochondria after selenite treatment, providing a mechanism for MUL1-regulated mitophagy. Co-immunoprecipitation, ubiquitination assay, subcellular fractionation, ULK1/ATG5 knockdown Autophagy Medium 26018823
2014 MUL1 E3 ligase interacts with four E2 ubiquitin-conjugating enzymes (Ube2E2, Ube2E3, Ube2G2, Ube2L3); the MUL1-Ube2E3 complex recruits GABARAP via an LC3-interacting region (LIR) in the MUL1 RING domain, linking MUL1 to mitophagy. Modified yeast two-hybrid screen with MUL1-E2 fusion proteins, Co-IP, LIR mutagenesis Cellular signalling Medium 25224329
2014 Omi/HtrA2 mitochondrial serine protease degrades Mulan/MUL1 as a specific substrate during oxidative stress; loss of Omi/HtrA2 protease activity causes MUL1 accumulation, decreased Mfn2 levels, and increased mitophagy. Substrate identification by protease assay, Omi/HtrA2 knockout MEFs and mnd2 mouse tissues, immunoblotting for Mfn2 and mitophagy markers Biochimica et biophysica acta Medium 24709290
2013 MUL1 localizes to mitochondria where it interacts with MAVS and catalyzes post-translational modifications of RIG-I that inhibit RIG-I-dependent NF-κB and IFN-β signaling; MUL1 depletion potentiates antiviral responses. Co-immunoprecipitation (MUL1-MAVS, MUL1-RIG-I), RNAi knockdown, NF-κB and IFN-β reporter assays, Sendai virus/poly I:C challenge Immunology and cell biology Medium 23399697
2017 MAPL/MUL1 is required for SUMOylation of RIG-I upon Sendai virus infection; RIG-I SUMOylation is a prerequisite for RIG-I activation and antiviral gene transcription. A constitutively active RIG-I bypasses the MAPL requirement. MAPL knockout (in vivo and in vitro), BioID proximity labeling, SUMOylation assay, constitutively active RIG-I epistasis Scientific reports High 28273895
2014 Mitochondrial hyperfusion promotes NF-κB activation through MULAN/MUL1 in a RING domain-dependent manner; MULAN forms a complex with TRAF2 and modulates its ubiquitylation as a transmitter of NF-κB signaling. Dominant-negative Drp1 overexpression, MARCH5 overexpression, MULAN knockdown, Co-IP of MULAN-TRAF2, NF-κB reporter assay The FEBS journal Medium 24841215
2018 MUL1 ubiquitinates HSPA5/GRP78 via K48-linked ubiquitination at lysine 446, leading to HSPA5 degradation and consequent lysosomal inhibition in head and neck cancer cells. Co-immunoprecipitation, K48-linked ubiquitination assay with K446 site mutation, MUL1 CRISPR knockout, Western blot Autophagy Medium 29260979
2019 MUL1 deficiency increases Mfn2 activity, triggering mitochondrial hyperfusion and acting as an ER-mitochondria tethering antagonist; reduced ER-Mito coupling elevates cytoplasmic Ca2+ which activates calcineurin and induces Drp1-dependent mitochondrial fragmentation and Parkin-mediated mitophagy. Overexpressing Mfn2 (not Mfn1) phenocopies MUL1 deficiency. MUL1 knockout neurons, live imaging of ER-Mito contacts, Ca2+ measurements, Mfn2 overexpression, PTPIP51 rescue, calcineurin inhibition Nature communications High 31409786
2019 The MUL1 RING domain adopts a ββαβ fold with a canonical cross-brace zinc-coordination motif; it interacts directly with the p53 transactivation domain 2 subdomain (residues 39-57) as determined by NMR chemical shift perturbation. NMR solution structure determination, NMR chemical shift perturbation experiments Biochemical and biophysical research communications High 31235254
2022 The MUL1 RING domain recruits both UBE2D2 and its substrate p53-TAD simultaneously; RING binding induces closed conformation of UBE2D2~Ub, and substrate binding affinity to the RING:UBE2D2~Ub complex is enhanced compared to either alone, explaining ubiquitylation of intrinsically disordered p53-TAD. Complex structure determination, oxyester mimetic UBE2D2~Ub assays, mutagenesis (N77A, S22R/C85S), binding affinity measurements The FEBS journal High 35048531
2020 MUL1 ubiquitinates UBXN7 (cofactor of the CRL2VHL ligase complex) via K48-linked ubiquitination; MUL1 inactivation leads to UBXN7 accumulation, increased HIF-1α levels, reduced oxidative phosphorylation, and increased glycolysis. Co-immunoprecipitation, ubiquitination assay, MUL1 knockout cells, metabolic flux analysis, mitochondrial respiration assay Scientific reports Medium 32005965
2020 MUL1 stabilizes PINK1 on the outer mitochondrial membrane in a gemcitabine-dependent manner, independently of mitochondrial depolarization, leading to Parkin-independent mitophagy. Gemcitabine treatment, PINK1 stabilization assay, MUL1 knockdown, mitophagy flux assay Scientific reports Medium 32001742
2022 MUL1 regulates Akt2 and HIF-1α protein levels through K48-specific polyubiquitination; absence of MUL1 leads to accumulation of both substrates and a metabolic shift from oxidative phosphorylation to glycolysis. MUL1 knockout cells, metabolomics, lipidomics, gene expression profiling, metabolic flux analysis, Akt2 KO cells, chemical inhibitors/activators Frontiers in cell and developmental biology Medium 35846359
2023 MAPL/MUL1 promotes Drp1 SUMOylation (SUMO1 modification) in the mitochondria, facilitating Drp1 mitochondrial translocation and mitochondrial fission; SENP5 negatively regulates Drp1 SUMOylation. MAPL overexpression/silencing, Drp1 SUMO-acceptor lysine mutation, AAV in vivo overexpression, SENP5 overexpression, mitochondrial fractionation Bone research Medium 40796734
2024 MAPL/MUL1 promotes SUMOylation of Drp1 in cardiomyocytes during sepsis; MAPL deficiency reduces Drp1 SUMOylation and Drp1 mitochondrial localization, ameliorating mitochondrial dysfunction and cardiac injury. Cardiomyocyte-specific MAPL KO mice, CLP sepsis model, SUMOylation assay, mitochondrial fractionation, membrane potential and ROS measurements Journal of translational medicine Medium 39529130
2024 MUL1 SUMOylates HSPA9 at lysine 612, causing HSPA9 export from mitochondria to the nucleus where it interacts with SUZ12 and EZH2, leading to their ubiquitination-mediated degradation and downstream STAT3 pathway inhibition to suppress bladder cancer lymph node metastasis. Co-IP with LC-MS/MS, SUMOylation proteomics, K612R HSPA9 point mutation, mitochondrial dissociation assay, confocal microscopy, in vivo xenograft International journal of biological sciences Medium 39113711
2025 MAPL/MUL1 induces pyroptosis through a pathway in which mitochondrial DNA is trafficked in mitochondrial-derived vesicles to lysosomes, which are permeabilized through gasdermin pores releasing mtDNA into the cytosol to activate cGAS; Parkinson's disease genes VPS35 and LRRK2 also regulate this MAPL-induced pyroptosis pathway. Genome-wide CRISPR functional screen, mtDNA trafficking assay, gasdermin pore assay, cGAS activation assay, primary macrophage depletion experiments Nature cell biology High 41083601
2023 MAPL loss in mice leads to increased bile acid production coupled with defective regulatory feedback; the peroxisomal bile acid transporter ABCD3 is a primary MAPL interacting partner and is SUMOylated in a MAPL-dependent manner. MAPL knockout mice, BioID proximity labeling, SUMOylation assay, primary hepatocyte cell-autonomous assays, metabolic profiling EMBO reports Medium 37962001
2023 MUL1 promotes degradation of cGAS by enhancing its interaction with MUL1 E3 ligase, a process mediated by HMGB1; GA disrupts HMGB1-cGAS interaction by inducing DOT1L-catalyzed methylation of HMGB1 at lysine 43, thereby promoting cGAS-MUL1 association and cGAS degradation. Co-immunoprecipitation, proteomics, pharmacological assays, scRNA-seq, ubiquitination assay Journal of translational medicine Low 41998635
2025 MUL1 ubiquitinates FUNDC1 to promote its proteasomal degradation, thereby reducing DRP1 expression and inhibiting DRP1-dependent mitophagy in cervical cancer cells. Co-immunoprecipitation, ubiquitination assay, MUL1 overexpression/knockdown, DRP1 knockdown rescue, xenograft model Journal of molecular histology Low 41697489
2025 SLC44A2 promotes MUL1-mediated ubiquitination and degradation of carnitine palmitoyltransferase 2 (CPT2) by enhancing the physical interaction between MUL1 and CPT2, without altering MUL1 expression levels, thereby inhibiting mitochondrial fatty acid oxidation. Co-immunoprecipitation, ubiquitination assay, SLC44A2 KO/overexpression, metabolic assays, in vivo xenograft Cell death & disease Low 40592838
2023 MUL1-mediated SUMOylation of NDP52 at lysine 262 via SUMO2 promotes recruitment of mitochondria to the autophagic pathway through early and recycling endosomal markers (EEA1, RAB11) and autophagy machinery components (ATG3, ATG5, ATG16L1, STX17), regulating mitophagy in cardiac hypertrophy. SUMOylation proteomics, isobaric quantitative proteomics, Co-IP with LC-MS/MS, NDP52 K262R point mutation, confocal microscopy, MUL1 overexpression Journal of cellular physiology Medium 37942585

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PloS one 641 18213395
2009 MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO reports 284 19407830
2016 Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. eLife 275 27852436
2015 MAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death. Molecular cell 272 26384664
2014 MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. eLife 263 24898855
2004 Mulan: multiple-sequence local alignment and visualization for studying function and evolution. Genome research 195 15590941
2012 The ubiquitin ligase Mul1 induces mitophagy in skeletal muscle in response to muscle-wasting stimuli. Cell metabolism 130 23140641
2015 Mitochondrial outer-membrane E3 ligase MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy. Autophagy 128 26018823
2019 Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts. Nature communications 125 31409786
2012 Akt is negatively regulated by the MULAN E3 ligase. Cell research 93 22410793
2016 Melatonin rescues zebrafish embryos from the parkinsonian phenotype restoring the parkin/PINK1/DJ-1/MUL1 network. Journal of pineal research 71 27064726
2014 Mulan E3 ubiquitin ligase interacts with multiple E2 conjugating enzymes and participates in mitophagy by recruiting GABARAP. Cellular signalling 71 25224329
2018 HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer. Autophagy 69 29260979
2008 GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth. Cell research 68 18591963
2021 The HSF1/miR-135b-5p axis induces protective autophagy to promote oxaliplatin resistance through the MUL1/ULK1 pathway in colorectal cancer. Oncogene 57 34140641
2014 Inactivation of Omi/HtrA2 protease leads to the deregulation of mitochondrial Mulan E3 ubiquitin ligase and increased mitophagy. Biochimica et biophysica acta 57 24709290
2015 Non-thermal plasma induces AKT degradation through turn-on the MUL1 E3 ligase in head and neck cancer. Oncotarget 50 26450902
2014 Mitochondrial hyperfusion promotes NF-κB activation via the mitochondrial E3 ligase MULAN. The FEBS journal 49 24841215
2020 Gemcitabine induces Parkin-independent mitophagy through mitochondrial-resident E3 ligase MUL1-mediated stabilization of PINK1. Scientific reports 46 32001742
2010 Molecular analysis of parasitoid linkages (MAPL): gut contents of adult parasitoid wasps reveal larval host. Molecular ecology 46 21083857
2013 Mitochondrially localised MUL1 is a novel modulator of antiviral signaling. Immunology and cell biology 40 23399697
2023 MuLan-Methyl-multiple transformer-based language models for accurate DNA methylation prediction. GigaScience 32 37489753
2022 Ginsenoside compound K protects against cerebral ischemia/reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy. Journal of ginseng research 32 37252276
2019 Defending stressed mitochondria: uncovering the role of MUL1 in suppressing neuronal mitophagy. Autophagy 26 31679452
2017 The dynamic interacting landscape of MAPL reveals essential functions for SUMOylation in innate immunity. Scientific reports 26 28273895
2020 Mitochondrial MUL1 E3 ubiquitin ligase regulates Hypoxia Inducible Factor (HIF-1α) and metabolic reprogramming by modulating the UBXN7 cofactor protein. Scientific reports 24 32005965
2022 Mitochondrial E3 ubiquitin ligase 1 (MUL1) as a novel therapeutic target for diseases associated with mitochondrial dysfunction. IUBMB life 23 35638168
2019 Effects of MUL1 and PARKIN on the circadian clock, brain and behaviour in Drosophila Parkinson's disease models. BMC neuroscience 19 31138137
2017 FOXO3 induces ubiquitylation of AKT through MUL1 regulation. Oncotarget 17 29299162
2019 Natural compound methyl protodioscin protects rat brain from ischemia/reperfusion injury through regulation of Mul1/SOD2 pathway. European journal of pharmacology 14 30716316
2022 Regulation of Metabolism by Mitochondrial MUL1 E3 Ubiquitin Ligase. Frontiers in cell and developmental biology 13 35846359
2022 Inhibition of Prostaglandin E2 Receptor EP3 Attenuates Oxidative Stress and Neuronal Apoptosis Partially by Modulating p38MAPK/FOXO3/Mul1/Mfn2 Pathway after Subarachnoid Hemorrhage in Rats. Oxidative medicine and cellular longevity 13 36531208
2019 MUL1 E3 ligase regulates the antitumor effects of metformin in chemoresistant ovarian cancer cells via AKT degradation. International journal of oncology 13 30816444
2014 C13orf18 and C1orf166 (MULAN) DNA genes methylation are not associated with cervical cancer and precancerous lesions of human papillomavirus genotypes in Iranian women. Asian Pacific journal of cancer prevention : APJCP 13 25169519
2012 Innate immune genes including a mucin-like gene, mul-1, induced by ionizing radiation in Caenorhabditis elegans. Radiation research 12 22967128
2023 NDP52 SUMOylation contributes to low-dose X-rays-induced cardiac hypertrophy through PINK1/Parkin-mediated mitophagy via MUL1/SUMO2 signalling. Journal of cellular physiology 11 37942585
2024 SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation. International journal of biological sciences 10 39113711
2019 Solution structure of MUL1-RING domain and its interaction with p53 transactivation domain. Biochemical and biophysical research communications 9 31235254
2022 MUL1-RING recruits the substrate, p53-TAD as a complex with UBE2D2-UB conjugate. The FEBS journal 8 35048531
2012 The missing link: Mul1 signals mitophagy and muscle wasting. Cell metabolism 8 23140636
2020 NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway. Neuropsychiatric disease and treatment 7 33116527
2023 MAPL loss dysregulates bile and liver metabolism in mice. EMBO reports 6 37962001
2022 Influence of melatonin associated with the Bio-Gide® membrane on osteoblast activity: an in vitro Study. Acta odontologica latinoamericana : AOL 6 36260939
2025 The mitochondrial E3 ligase MAPL SUMOylates Drp1 to facilitate mitochondrial fission in intervertebral disc degeneration. Bone research 5 40796734
2025 MAPL regulates gasdermin-mediated release of mtDNA from lysosomes to drive pyroptotic cell death. Nature cell biology 5 41083601
2024 Deletion of MAPL ameliorates septic cardiomyopathy by mitigating mitochondrial dysfunction. Journal of translational medicine 5 39529130
2023 Myristate induces mitochondrial fragmentation and cardiomyocyte hypertrophy through mitochondrial E3 ubiquitin ligase MUL1. Frontiers in cell and developmental biology 5 37051468
2019 MUL1 gene polymorphisms and Parkinson's disease risk. Acta neurologica Scandinavica 5 30793286
2015 The Evolutionary History of MAPL (Mitochondria-Associated Protein Ligase) and Other Eukaryotic BAM/GIDE Domain Proteins. PloS one 5 26047467
2012 MULAN related gene (MRG): a potential novel ubiquitin ligase activator of NF-kB involved in immune response in Atlantic salmon (Salmo salar). Developmental and comparative immunology 5 22989998
2011 Cloning and expression analysis of the mitochondrial ubiquitin ligase activator of NF-κB (MULAN) in Atlantic salmon (Salmo salar). Molecular immunology 5 22056942
2025 SLC44A2 negatively regulates mitochondrial fatty acid oxidation to suppress colorectal progression by blocking the MUL1-CPT2 interaction. Cell death & disease 4 40592838
2024 Inactivation of mitochondrial MUL1 E3 ubiquitin ligase deregulates mitophagy and prevents diet-induced obesity in mice. Frontiers in molecular biosciences 4 38725872
2008 MICROPATTERNING OF GOLD SUBSTRATES BASED ON POLY(PROPYLENE SULFIDE-BL-ETHYLENE GLYCOL), (PPS-PEG) BACKGROUND PASSIVATION AND THE MOLECULAR-ASSEMBLY PATTERNING BY LIFT-OFF (MAPL) TECHNIQUE. Surface science 4 19578480
2025 MULAN: multimodal protein language model for sequence and structure encoding. Bioinformatics advances 2 40989496
2024 MUL1 identified as mitochondria-linked biomarker promoting cisplatin resistance in OC cells. Gene 2 39134101
2024 Increased ROS levels in mitochondrial outer membrane protein Mul1-deficient oocytes result in abnormal preimplantation embryogenesis. FEBS letters 1 38639871
2015 Retraction Notice to: The Ubiquitin Ligase Mul1 Induces Mitophagy in Skeletal Muscle in Response to Muscle-Wasting Stimuli. Cell metabolism 1 26973995
2026 MUL1 suppresses cervical cancer progression by targeting FUNDC1 for ubiquitination and inhibiting DRP1-dependent mitophagy. Journal of molecular histology 0 41697489
2026 Glypican-3 Upregulated by YTHDF1 in an m6A-Dependent Manner Interacts With MUL1 to Repress HSF1 Ubiquitination Degradation, Boost CD276 Transcription, and Mediate Immune Escape in Gastric Cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41944736
2026 18-β-glycyrrhetinic acid facilitates nuclear-mitochondrial communications to alleviate oxidative stress through HMGB1-cGAS-Mul1 axis in tendinopathy. Journal of translational medicine 0 41998635
2025 The tumor suppressor role of mitochondrial E3 ubiquitin ligase MUL1 in osteosarcoma. Biochimica et biophysica acta. Molecular cell research 0 41468924
2023 Retraction: Protective effect of hsa-miR-570-3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway. Li-Li Wang, Wei-Wei Huang, Jing Huang, Rong-Fang Huang, Na-Ni Li, Yi Hong, Mu-Lan Chen, Fan Wu, Jian Liu, Kaohsiung J Med Sci. 2020; 36(8): 581-591 (https://doi.org/10.1002/kjm2.12212). The Kaohsiung journal of medical sciences 0 38088487