Affinage

MARCHF5

E3 ubiquitin-protein ligase MARCHF5 · UniProt Q9NX47

Length
278 aa
Mass
31.2 kDa
Annotated
2026-06-10
81 papers in source corpus 50 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MARCHF5 (MITOL/MARCH5) is a RING-type E3 ubiquitin ligase anchored in the mitochondrial outer membrane that maintains mitochondrial and cellular homeostasis by ubiquitinating a broad substrate repertoire (PMID:16936636, PMID:17606867). Its central role is controlling mitochondrial dynamics: it ubiquitinates Drp1 and regulates its assembly/disassembly at fission sites (PMID:16936636, PMID:17606867), degrades the Drp1 receptor MiD49 and the fission factor MIEF2 to restrain fission (PMID:26564796, PMID:41353882), and ubiquitinates the fusion mediators Mfn1 (degradative, including cell-cycle- and acetylation-dependent control) and Mfn2 (K63-linked at K192 to drive oligomerization and ER–mitochondria tethering) (PMID:20103533, PMID:23253261, PMID:23727017, PMID:24722297). MARCHF5 governs innate immune signaling, resolving MAVS aggregates and active RIG-I oligomers through K48-linked degradative ubiquitination to terminate antiviral signaling (PMID:26246171, PMID:31881323), activating TANK via K63-linked chains to promote NF-κB signaling (PMID:21625535), and K27-ubiquitinating NLRP3 at K324/K430 to enable inflammasome assembly (PMID:37575012). It sets the apoptotic threshold by controlling MCL1 stability in a NOXA/MTCH2/UBE2K-dependent manner and by restraining BAK activating conformation changes (PMID:26910119, PMID:32094511, PMID:36171332). MARCHF5 directs mitochondrial quality control and mitophagy through hypoxia-induced FUNDC1 degradation at K119, Parkin ubiquitination at K220, K6-linked ubiquitination of the mtDNA import substrates PolγA and RECQL4, and K48-linked degradation of MIC60 (PMID:28104734, PMID:33565245, PMID:33657094, PMID:37495109, PMID:37679468), and at the MAM it K63-ubiquitinates IRE1α at K481 to prevent hyper-oligomerization and limit RIDD-driven apoptosis (PMID:31368599). Beyond mitochondria, MARCHF5 localizes to peroxisomes via PEX19 and is essential for de novo peroxisome biogenesis, transferring peroxins such as Pex26 and ubiquitinating PMP70 (PMID:34747980, PMID:39423819, PMID:39423820, PMID:42182360). In vivo, MARCHF5 loss produces mitochondrial fragmentation, senescence, and heart failure, ferroptosis susceptibility, β-cell dysfunction via a Trim28/Kindlin-2/MafA axis, and cardiac hypertrophy through Akt signaling (PMID:35789860, PMID:34390730, PMID:40750777, PMID:40753540).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2006 High

    Established that MARCH5 is an outer mitochondrial membrane E3 ligase coupling ubiquitination to mitochondrial shape, answering whether a dedicated ligase regulates fission/fusion machinery.

    Evidence Reciprocal Co-IP, RING-mutant expression, and mitochondrial morphology imaging showing MFN2/Drp1 binding and Drp1 ubiquitination

    PMID:16936636

    Open questions at the time
    • Linkage type and direct substrate sites on Drp1 not defined
    • Whether Drp1 ubiquitination is degradative or regulatory unresolved
  2. 2007 High

    Showed the RING domain controls Drp1 trafficking and assembly at fission sites, defining MARCH5 as a dynamic regulator rather than a constitutive degrader of Drp1.

    Evidence RING mutagenesis, RNAi, FRAP of YFP-Drp1, and rescue epistasis with Drp1 vs Fis1

    PMID:17606867

    Open questions at the time
    • Molecular detail of how ubiquitination alters Drp1 mobility not resolved
  3. 2010 High

    Identified Mfn1 as a major degradative substrate and linked MARCH5 activity to suppression of mitochondrial elongation and cellular senescence.

    Evidence shRNA knockdown, GTPase-deficient Mfn1 rescue, SA-β-Gal senescence assay

    PMID:20103533

    Open questions at the time
    • Ubiquitination site on Mfn1 not mapped here
  4. 2009 High

    Demonstrated MARCH5 acts in mitochondrial protein quality control by selectively ubiquitinating misfolded substrates (mutant SOD1), extending its role beyond dynamics.

    Evidence In vitro ubiquitination, cycloheximide chase, siRNA knockdown, ROS measurement

    PMID:19741096 PMID:20851218

    Open questions at the time
    • Recognition mechanism distinguishing misfolded from native substrates unclear
  5. 2013 High

    Resolved how MARCH5 promotes ER–mitochondria contacts, showing non-degradative K63 ubiquitination of Mfn2 at K192 activates GTP-dependent oligomerization for MAM tethering.

    Evidence Domain-mapping mutagenesis, K63-linkage assay, blue-native PAGE, GTP binding/hydrolysis assays

    PMID:23727017

    Open questions at the time
    • How MARCH5 switches between K63-regulatory and K48-degradative outputs not established
  6. 2015 High

    Defined MARCH5 as a brake on antiviral signaling by degrading MAVS aggregates, linking mitochondrial ubiquitination to interferon control in vivo.

    Evidence Site-specific (K7/K500) ubiquitination assay, March5+/- mice, IFN and viral replication readouts

    PMID:26246171

    Open questions at the time
    • How MARCH5 selectively recognizes aggregated vs monomeric MAVS not fully defined
  7. 2015 High

    Extended innate immune regulation to positive signaling and stem-cell biology, showing K63 ubiquitination of TANK promotes NF-κB and K63 ubiquitination of Prkar1a maintains pluripotency.

    Evidence Linkage-specific and site-specific ubiquitination assays, NF-κB reporter, PKA activity readouts, reprogramming assays

    PMID:21625535 PMID:26033541

    Open questions at the time
    • How MARCH5 outputs are wired to opposing immune outcomes (activation vs termination) is unresolved
  8. 2015 High

    Identified MiD49 as a degradative substrate and self-clearance via homodimerization, clarifying how MARCH5 limits fission and controls its own abundance.

    Evidence MARCH5/MiD49 double knockout epistasis, GxxxG dimerization mutants, cycloheximide chase

    PMID:26476016 PMID:26564796

    Open questions at the time
    • Quantitative balance between MiD49 and Drp1 outputs in setting fission rate not defined
  9. 2016 High

    Mapped a degradation complex requiring the MARCH5 C-terminus, Mff, and p97/Npl4 for substrate release from the OMM, explaining the extraction step downstream of ubiquitination.

    Evidence Drp1/Mff knockout and double-knockout cells, Co-IP of complex components, half-life measurements

    PMID:27932492

    Open questions at the time
    • Structural basis of substrate handoff to p97 not determined
  10. 2016 High

    Established MARCH5 as the principal regulator of MCL1 stability in a NOXA/MTCH2/UBE2K-dependent manner, defining an apoptotic threshold relevant to BH3-mimetic resistance.

    Evidence Chemical/genetic MARCH5 perturbation, genome-wide CRISPR screen, NOXA-dependency, MCL1 ubiquitination/stability assays

    PMID:26910119 PMID:32094511 PMID:32484436

    Open questions at the time
    • How NOXA binding licenses MCL1 for MARCH5 recognition mechanistically unresolved
  11. 2017 High

    Connected antiviral signaling to mitophagy regulation: PKAC-mediated MAVS phosphorylation primes K48 degradation, and hypoxia-induced FUNDC1 ubiquitination at K119 fine-tunes mitophagy.

    Evidence Phospho-site (T54A) and K119 site-specific mutants, linkage-specific ubiquitination, mitophagy flux assays

    PMID:28104734 PMID:28934360

    Open questions at the time
    • Spatial coordination of these stress-specific substrate choices not defined
  12. 2019 High

    Defined MARCH5 control of the ER stress response and mitophagy initiation, K63-ubiquitinating IRE1α at K481 to limit RIDD and providing the initial ubiquitin substrate for PINK1/Parkin recruitment.

    Evidence K481R and linkage-specific assays, MITOL KO cells and mice, RIDD activity, Parkin recruitment assays

    PMID:31110043 PMID:31368599

    Open questions at the time
    • Identity of the initial PINK1-phosphorylated ubiquitin substrate provided by MARCH5 not pinpointed
  13. 2019 High

    Extended antiviral termination to direct degradation of active RIG-I oligomers, establishing dual RIG-I/MAVS targeting to switch off RLR signaling.

    Evidence K48-linkage site-specific (K193/K203) ubiquitination, proteasome rescue, oligomer analysis

    PMID:31881323

    Open questions at the time
    • Temporal sequence of RIG-I vs MAVS targeting during infection not resolved
  14. 2021 High

    Revealed MARCH5 dual localization to peroxisomes via PEX19 and its role in PMP70 ubiquitination and pexophagy, broadening its organellar reach.

    Evidence PUP-IT proximity tagging, Co-IP, MARCH5 KO, pexophagy assays

    PMID:34747980

    Open questions at the time
    • Determinants directing MARCH5 to peroxisomes vs mitochondria not defined here
  15. 2021 High

    Defined MARCH5 control over mtDNA maintenance and mitophagy fine-tuning via K6-linked ubiquitination of PolγA (K1060) and Parkin (K220), gating mitochondrial import and Parkin turnover.

    Evidence In vitro and K6-linkage-specific ubiquitination, site-specific mutants, Tom20 binding and mtDNA replication assays, PEO/patient mutant analysis

    PMID:33565245 PMID:33657094

    Open questions at the time
    • How K6 linkage is decoded to block Tom20-mediated import mechanistically unclear
  16. 2021 High

    Linked MARCH5 to cardiac homeostasis in vivo, showing its loss causes Drp1-driven fragmentation, senescence, heart failure, and ferroptosis susceptibility via reduced mitochondrial GPX4.

    Evidence Cardiomyocyte-specific conditional KO mice, MI and doxorubicin models, AAV rescue, GSH/GSSG and lipid peroxidation assays

    PMID:33970775 PMID:34390730 PMID:35789860

    Open questions at the time
    • Whether ferroptosis protection is direct GPX4 regulation or secondary to dynamics unresolved
  17. 2022 High

    Established MARCH5 restrains BAK activating conformation independently of BH3-only proteins, defining an apoptosis-suppressive function beyond MCL1 turnover.

    Evidence Genome-wide CRISPR screen, multiple cell lines, BAK conformation and BH3-mimetic response assays

    PMID:36171332

    Open questions at the time
    • Whether BAK restraint is via direct ubiquitination or indirect not determined
  18. 2023 High

    Expanded immune regulation to NLRP3 inflammasome and STING control, with K27 ubiquitination enabling NLRP3-NEK7 assembly and STING ubiquitination preventing oxidation-induced inactive polymers.

    Evidence Site-specific (K324/K430) K27-linkage assays, myeloid conditional KO mice, STING polymer/ROS analyses

    PMID:37575012 PMID:37916870 PMID:38040710

    Open questions at the time
    • How K27 chains are decoded to template inflammasome oligomerization is unclear
  19. 2023 High

    Added MIC60 (K48 at K285), RECQL4 (K6 at K1101/K1154), and γc cytokine receptor (K27) as substrates, linking MARCH5 to cristae integrity, mtDNA import, and T-cell cytokine signaling.

    Evidence Site-specific linkage assays, TRAP1 competition, RTS patient mutants, PD-1/BATF-dependent γc degradation

    PMID:37495109 PMID:37679468 PMID:37932447

    Open questions at the time
    • Coordination of these distinct linkage outputs on different substrates not unified
  20. 2024 High

    Established an essential role in de novo peroxisome biogenesis from mitochondria, with MARCH5 acting upstream of Pex14 and degrading MPC1 to promote glycolysis.

    Evidence Multiple/double KO epistasis (Pex14, Pex3), fatty-acid-induced biogenesis, activity-mutant accumulation on pre-peroxisomes, metabolic OCR/ECAR assays

    PMID:38615083 PMID:39423819 PMID:39423820

    Open questions at the time
    • Substrates ubiquitinated during the mitochondrial steps of biogenesis incompletely defined
  21. 2025 High

    Defined an in vivo β-cell signaling axis (Trim28/Kindlin-2/MafA) and cardiac hypertrophy via Akt, plus K27 ubiquitination of JEV envelope protein, broadening MARCH5 into endocrine, cardiac, and viral-host contexts.

    Evidence β-cell and cardiac conditional/heterozygous KO mice, epistasis rescue, Co-IP, site-specific viral E-protein ubiquitination assays

    PMID:40071916 PMID:40750777 PMID:40753540

    Open questions at the time
    • Whether Akt phosphorylation enhancement is direct or via a substrate intermediary unresolved
  22. 2026 Medium

    Linked DAPK1-mediated Parkin phosphorylation to MARCH5-dependent Parkin degradation in neurotoxicity, integrating phospho-signaling with the K220 ubiquitination event.

    Evidence Phospho-site mutants (S136A/S198A), Co-IP, ubiquitination assay, 6-OHDA neurotoxicity model

    PMID:41943176

    Open questions at the time
    • Single-lab; how phosphorylation directs Parkin to MITOL not structurally defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MARCH5 selects among dozens of substrates and assembles distinct ubiquitin linkage types (K6, K27, K48, K63) with opposing regulatory vs degradative outcomes at specific subcellular sites remains unresolved.
  • No unifying substrate-recognition or linkage-determination model
  • Structural basis for linkage-type specificity unknown
  • Coordination of mitochondrial vs peroxisomal pools not mechanistically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 8 GO:0016874 ligase activity 3
Localization
GO:0005777 peroxisome 3 GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-168256 Immune System 6 R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-9612973 Autophagy 4 R-HSA-8953897 Cellular responses to stimuli 1
Partners
DRP1FUNDC1MAVSMCL1MFN1MFN2MID49MTCH2
Complex memberships
MARCH5 homodimerMARCH5/p97/Npl4 degradation complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 MARCH5 (MARCH-V) is a transmembrane E3 ubiquitin ligase of the mitochondrial outer membrane that binds mitofusin 2 (MFN2) and ubiquitinated forms of Drp1 by co-immunoprecipitation, promotes ubiquitination of Drp1, and overexpression promotes formation of long tubular mitochondria in a MFN2-dependent manner; RING finger mutations cause mitochondrial fragmentation. Co-immunoprecipitation, overexpression and RING-mutant expression, mitochondrial morphology imaging EMBO reports High 16936636
2007 MARCH5 RING domain activity is required for Drp1-dependent mitochondrial fission; RING mutants cause mitochondrial elongation reversed by ectopic Drp1 but not Fis1; MARCH5 regulates subcellular trafficking of Drp1 (assembly/disassembly at fission sites) as shown by abnormal Drp1 clustering and reduced YFP-Drp1 mobility in MARCH5 RING mutant cells; MARCH5 RING mutants and endogenous Drp1 co-assemble into enlarged clusters in a Drp1 GTPase-dependent manner. RING domain mutagenesis, RNAi knockdown, FRAP of YFP-Drp1, co-immunoprecipitation, mitochondrial morphology imaging, rescue epistasis The Journal of cell biology High 17606867
2009 MITOL/MARCH5 interacts with and ubiquitinates mutant SOD1 (mSOD1) but not wild-type SOD1 in mitochondria; in vitro ubiquitination assay confirmed direct ubiquitination; MITOL overexpression promotes mSOD1 degradation and suppresses mitochondrial mSOD1 accumulation and mSOD1-induced ROS generation; MITOL knockdown or CS-mutant expression increases mSOD1 accumulation, ROS, and cell death. Co-immunoprecipitation, in vitro ubiquitination assay, cycloheximide-chase, siRNA knockdown, ROS measurement Molecular biology of the cell High 19741096
2010 MARCH5 knockdown causes accumulation of elongated, interconnected mitochondria and cellular senescence (SA-β-Gal activity); Mfn1 levels specifically increase in MARCH5-depleted cells identifying Mfn1 as a major ubiquitylation substrate; introduction of GTPase-deficient Mfn1(T109A) abolishes both mitochondrial elongation and senescence; ectopic Drp1 (but not Fis1) rescues mitochondrial morphology and reduces senescence. shRNA knockdown, RING domain mutant expression, SA-β-Gal assay, rescue epistasis, western blot for substrate levels Journal of cell science High 20103533
2010 MITOL/MARCH5 promotes degradation of polyglutamine-expanded ataxin-3 (ΔNAT-3Q71) via the ubiquitin-proteasome pathway; MITOL knockdown induces accumulation of detergent-insoluble polyQ aggregates, cytochrome c release, and cell death. Co-immunoprecipitation, overexpression, siRNA knockdown, cycloheximide chase, cytochrome c release assay Mitochondrion Medium 20851218
2011 MARCH5 positively regulates TLR7 signaling by interacting with TANK and catalyzing K63-linked poly-ubiquitination of TANK at Lys229, 233, 280, 302, and 306, thereby impairing TANK's ability to inhibit TRAF6 and enhancing NF-κB-mediated gene expression; mitochondrial localization of MARCH5 is required for this effect. Co-immunoprecipitation, in vivo ubiquitination assay with linkage-specific ubiquitin mutants, site-directed mutagenesis, MARCH5 mislocalization construct, NF-κB reporter assay PLoS pathogens High 21625535
2012 MITOL/MARCH5 ubiquitinates S-nitrosylated MAP1B-light chain 1 (LC1); S-nitrosylation of LC1 causes a conformational change that both activates LC1 and promotes its ubiquitination by MITOL, linking microtubule stabilization to MITOL; excessive NO inhibits MITOL, leading to accumulation of S-nitrosylated LC1 and neuronal cell death. Co-immunoprecipitation, in vitro ubiquitination, MITOL knockdown, NO stimulation, mitochondrial dysfunction readouts Proceedings of the National Academy of Sciences of the United States of America High 22308378
2012 Mfn1 is degraded through MARCH5-mediated ubiquitylation specifically in G2/M phase; Mfn1 interacts with cyclin B1 and their interaction is stronger in G2/M phase, suggesting cyclin B1/Cdk1 facilitates MARCH5-mediated Mfn1 degradation during mitotic entry. Co-immunoprecipitation, western blot for protein levels at cell cycle stages, ubiquitylation assay Cell division Medium 23253261
2013 MITOL/MARCH5 regulates MAM (mitochondria-associated ER membrane) domain formation through mitofusin 2 (Mfn2): MITOL interacts with mitochondrial Mfn2 (not ER-associated Mfn2) via MITOL C-terminal domain and Mfn2 HR1 domain; MITOL mediates K63-linked polyubiquitin chain addition to Mfn2 at K192 (identified by mutation analysis) without proteasomal degradation; this K192 ubiquitination activates GTP-dependent Mfn2 oligomerization required for ER-mitochondria tethering. Co-immunoprecipitation, domain mapping mutagenesis, K63-linkage-specific ubiquitin assay, sucrose-density gradient centrifugation, blue-native PAGE, GTP binding/hydrolysis assay, MITOL knockdown with MAM function readout Molecular cell High 23727017
2014 MARCH5 binds Mfn1 and mediates its ubiquitylation; acetylated Mfn1 (at K491) shows enhanced interaction with MARCH5 and increased ubiquitylation; acetylation-deficient Mfn1(K491R) shows reduced MARCH5 binding and ubiquitylation; MARCH5-knockout MEFs and MARCH5(H43W)-expressing cells undergo rapid cell death under mitochondrial stress, demonstrating that MARCH5-mediated quality control on acetylated Mfn1 is required for cell survival. Co-immunoprecipitation, ubiquitylation assay, acetylation-deficient and mimetic mutants, MARCH5 knockout MEFs, cell death assay Cell death & disease High 24722297
2015 MARCH5 controls Drp1-dependent mitochondrial fission and cell sensitivity to stress-induced apoptosis by selectively ubiquitinating and targeting MiD49 (a mitochondrial Drp1 receptor) for proteasomal degradation; MARCH5 knockout causes MiD49 accumulation and mitochondrial fragmentation; MiD49 knockout in MARCH5-/- cells reverses fragmentation and reduces apoptosis sensitivity. MARCH5 knockout, MiD49 knockout, ubiquitination assay, proteasome inhibitor experiments, mitochondrial morphology imaging, apoptosis assay, rescue epistasis Molecular biology of the cell High 26564796
2015 MARCH5 forms homodimers through a GxxxG dimerization motif (first motif critical); dimerization-defective MARCH5(4GL) mutant cannot degrade accumulated inactive MARCH5 mutants, showing that MARCH5 self-clearance via ubiquitin-proteasome pathway requires homodimerization; inactive MARCH5 mutants have ~4-fold longer half-life and accumulation activates NF-κB. Co-immunoprecipitation, dimerization motif mutagenesis, cycloheximide chase, NF-κB reporter assay The FEBS journal Medium 26476016
2015 MARCH5 is the mitochondrial E3 ligase that resolves MAVS aggregates during antiviral signaling; MARCH5 binds MAVS only when MAVS forms aggregates during viral stimulation, requiring MARCH5 RING domain and MAVS CARD domain; MARCH5 transfers ubiquitin to MAVS at Lys7 and Lys500 promoting proteasomal degradation; March5+/- mice show elevated type-I interferon responses and reduced viral replication. Co-immunoprecipitation, in vivo ubiquitination assay with site-specific mutants, March5+/- mouse model, IFN response measurement, viral replication assay Nature communications High 26246171
2015 March5, as a transcriptional target of Klf4, maintains mouse ESC pluripotency by catalyzing K63-linked polyubiquitination of Prkar1a (a negative regulatory subunit of PKA), thereby activating PKA and inhibiting the Raf/MEK/ERK pathway. March5 knockdown/overexpression in mESCs, K63-ubiquitin assay, PKA activity measurement, ERK pathway readouts, rescue experiments, somatic cell reprogramming Nature communications High 26033541
2016 MARCH5 C-terminal domain plays a critical role in degradation of MARCH5 substrates (MiD49 and Mcl1), likely by facilitating release of ubiquitinated proteins from the OMM; Drp1 and Mff negatively regulate MARCH5 activity toward MiD49 and Mcl1, as knockout of either leads to reduced expression and increased ubiquitination of these substrates; Mff is an integral component of the MARCH5/p97/Npl4 degradation complex. Drp1/Mff knockout cells, double knockout (Drp1-/-/MARCH5-/- and Mff-/-/MARCH5-/-), ubiquitination assays, co-immunoprecipitation, half-life measurements Molecular biology of the cell High 27932492
2016 MARCH5 inhibition abrogates MCL1-dependent resistance to BH3 mimetic ABT-737 through NOXA-dependent regulation of MCL1 ubiquitylation and stability; MARCH5 controls MCL1 ubiquitylation in a NOXA-dependent manner. Chemical inhibition and genetic knockdown of MARCH5, MCL1 ubiquitylation assay, NOXA-dependency rescue experiments, cancer cell apoptosis assay Oncotarget Medium 26910119
2017 MARCH5 ubiquitylates and degrades FUNDC1 (a mitophagy receptor) specifically in response to hypoxia, targeting K119 of FUNDC1; MARCH5 directly interacts with FUNDC1, and this interaction is enhanced by hypoxic stress; MARCH5-mediated FUNDC1 degradation fine-tunes hypoxia-induced mitophagy; MARCH5 knockdown causes FUNDC1 accumulation and exaggerated mitophagy. Co-immunoprecipitation, in vivo ubiquitination assay with K119 site-specific mutant, MARCH5 knockdown/overexpression, mitophagy flux measurement EMBO reports High 28104734
2017 PKACs (protein kinase A catalytic subunits) phosphorylate MAVS/VISA at T54, abrogating virus-induced MAVS aggregation and priming it for K48-linked polyubiquitination and proteasomal degradation by MARCH5; phosphorylation at T54 is required for MARCH5-mediated MAVS degradation. Co-immunoprecipitation, in vivo ubiquitination assay, phosphorylation-site mutant (T54A), PKAC inhibitor H89, antiviral signaling assays PLoS pathogens High 28934360
2019 MITOL/MARCH5 ubiquitylates IRE1α at K481 with K63-linked chains at the MAM, preventing IRE1α hyper-oligomerization and RIDD activity; MITOL depletion or IRE1α K481R mutant allows hyper-oligomerization and enhanced RIDD, resulting in apoptosis; in spinal cord of MITOL-deficient mice, ER stress enhances RIDD activity and apoptosis. Co-immunoprecipitation, K63-linkage ubiquitination assay, K481R site-specific mutant, MITOL knockout cells and mice, RIDD activity assay, IRE1α oligomerization assay The EMBO journal High 31368599
2019 MITOL/MARCH5 facilitates initial Parkin recruitment to impaired mitochondria by providing ubiquitin substrate for PINK1-mediated phosphorylation; depletion of MITOL/MARCH5 delays Parkin recruitment and activation on damaged mitochondria. MITOL/MARCH5 depletion, Parkin recruitment assay, mitochondrial damage model The Journal of biological chemistry Medium 31110043
2019 MARCH5 targets and degrades active RIG-I (but not its inactive phosphomimetic form RIG-IS8E) via K48-linked polyubiquitination at Lys193 and Lys203 of RIG-I; MARCH5 RING domain binds RIG-I CARD domain; co-expression of MARCH5 reduces RIG-I oligomers; dual targeting of RIG-I and MAVS by MARCH5 turns off RLR signaling. Co-immunoprecipitation, in vivo K48-ubiquitination assay with site-specific mutants, proteasome inhibitor rescue, poly(I:C) stimulation, oligomer analysis Cellular signalling High 31881323
2019 MARCH5 interacts with HBx protein in mitochondria via its N-terminal RING domain, targets HBx for proteasomal degradation, and eliminates HBx protein aggregates; MARCH5 lacking E3 ligase activity (H43W) fails to reduce HBx levels; MARCH5-mediated HBx degradation suppresses HBx-induced ROS, mitophagy, and COX-2 expression. Co-immunoprecipitation, ubiquitination assay, RING domain mutant (H43W), proteasome inhibitor, semi-denaturing detergent agarose gel for aggregates, ROS measurement Cell death & disease Medium 31819032
2020 MARCH5 is the primary mediator of NOXA-dependent MCL1 degradation in prostate cancer cells; increased NOXA (via kinase inhibitor-induced integrated stress response) drives MARCH5-mediated MCL1 degradation, enhancing apoptosis in response to BH3 mimetics. MARCH5 genetic manipulation, NOXA overexpression/knockdown, MCL1 ubiquitination and stability assays, apoptosis with BH3 mimetics eLife Medium 32484436
2020 MARCH5, UBE2K (E2), and MTCH2 (outer mitochondrial membrane protein) co-operate to mark MCL1 for proteasomal degradation specifically when MCL1 is bound by NOXA; degradation requires the MCL1 transmembrane domain and specific MCL1 lysine residues; MTCH2 is essential for MARCH5-mediated MCL1:NOXA complex turnover. Genome-wide CRISPR-Cas9 screen, genetic validation of MARCH5, UBE2K, MTCH2 knockouts, MCL1 ubiquitination and stability assays, NOXA-dependency experiments Cell death and differentiation High 32094511
2020 MARCH5 determines the initial MCL1-NOXA levels upon mitotic entry; MARCH5 knockout paradoxically enhances mitotic apoptosis in a BAK-dependent manner independently of MCL1 and other BH3-only proteins; DRP1 disruption reduces mitotic apoptosis in MARCH5-disrupted cells, linking mitochondrial fission maintenance to the pro-apoptotic role of MARCH5 loss. MARCH5 knockout, MCL1 knockout, BAK knockout, DRP1 knockout, mitotic apoptosis assays Cell death and differentiation Medium 32015503
2020 MARCHF5/MARCH5 is degraded by chaperone-mediated autophagy (CMA) via interaction with key CMA regulators (HSPA8, LAMP2A); severe oxidative stress compromises CMA activity, stabilizing MARCHF5, which facilitates DRP1 translocation and excessive mitochondrial fission; increasing CMA activity promotes MARCHF5 turnover, reduces DRP1 translocation, and reduces mitochondrial fragmentation. CMA substrate identification, Co-IP with CMA regulators, lysosomal degradation assay, MARCHF5 stability measurement, DRP1 translocation assay, mitochondrial morphology imaging, PD rodent model Autophagy Medium 33970775
2021 MARCH5 localizes to peroxisomes (in addition to mitochondria) via PEX19 binding to its transmembrane region; on peroxisomes, MARCH5 binds and mediates ubiquitination of PMP70; PMP70 ubiquitination and mTOR-inhibition-induced pexophagy are blocked in the absence of MARCH5. PUP-IT proximity tagging, co-immunoprecipitation, subcellular fractionation and imaging, ubiquitination assay, MARCH5 knockout, pexophagy assay The Journal of cell biology High 34747980
2021 MITOL/MARCH5 promotes proteasomal degradation of Parkin by ubiquitinating Parkin at K220, fine-tuning mitophagy; MITOL deletion leads to accumulation of phosphorylated active Parkin in the ER, causing FKBP38 degradation and enhanced cell death; MITOL undergoes FKBP38-dependent translocation from mitochondria to ER during mitophagy. Co-immunoprecipitation, K220 site-specific ubiquitination assay, MITOL knockout cells, subcellular fractionation imaging, cell death assay EMBO reports High 33565245
2021 MITOL/MARCH5 ubiquitylates PolγA (mitochondrial DNA polymerase) at K1060 via K6-linked ubiquitin chain; this ubiquitylation negatively regulates PolγA binding to Tom20 and its entry into mitochondria; certain PEO patient PolγA mutants are hyperubiquitylated by MITOL and fail to enter mitochondria, compromising mtDNA replication. Co-immunoprecipitation, in vitro ubiquitination assay, K6-linkage-specific ubiquitin assay, Tom20 binding assay, mitochondrial import assay, BrdU incorporation into mtDNA PLoS biology High 33657094
2021 MITOL/MARCH5 cardiac-specific knockout mice develop mitochondrial fragmentation, dysfunction (reduced ATP, increased ROS), myocardial senescence, and chronic heart failure through persistent Drp1 accumulation; AAV-mediated MITOL gene delivery ameliorates cardiac dysfunction after MI. Cardiomyocyte-specific conditional knockout mice, mitochondrial morphology and function assays, in vivo MI model, AAV gene delivery iScience High 35789860
2021 MITOL/MARCH5 knockdown in cardiomyocytes (NRVMs) reduces mitochondria-localized GPX4, decreasing GSH/GSSG ratio and promoting lipid peroxide accumulation leading to ferroptosis; MITOL knockdown increases CHAC1 (GSH-degrading enzyme) expression; cardiac-specific MITOL knockout mice show enhanced susceptibility to doxorubicin-induced ferroptosis. siRNA knockdown, cardiac-specific MITOL KO mice, GPX4 expression analysis, GSH/GSSG measurement, lipid peroxidation assay, ferroptosis inhibitor (ferrostatin-1) rescue Journal of molecular and cellular cardiology High 34390730
2022 MARCHF5/MITOL loss drives BAK to adopt an activated conformation independently of BH3-only proteins, forming inhibitory complexes with MCL-1 and BCL-XL, conferring resistance to BH3-mimetic drugs; MARCHF5 restrains BAK activating conformation change. Genome-wide CRISPR-Cas9 screen, MARCHF5 deletion in multiple cell lines, BAK conformation assay, BH3-mimetic drug response assay, co-immunoprecipitation Cell death and differentiation High 36171332
2022 MITOL/MARCH5 interacts with and ubiquitinates RMDN3/PTPIP51 at K89, activating its phosphatidic acid (PA)-binding and transfer activity; loss of MITOL or K89R substitution in RMDN3 significantly reduces PA-binding activity at the mitochondria-ER contact site. APEX2 proximity labeling, co-immunoprecipitation, K89 site-specific ubiquitination assay, PA-binding activity assay, MITOL knockout Journal of biochemistry Medium 34964862
2022 In the context of CMT2A-linked MFN2 R364W mutation, MITOL shows weaker interaction with R364W-MFN2 than wild-type MFN2, making MITOL more available for DRP1 ubiquitylation; this leads to multi-monoubiquitylation and proteasomal degradation of DRP1 resulting in mitochondrial hyperfusion. Co-immunoprecipitation comparing WT vs R364W MFN2, ubiquitylation assay, DRP1 stability assay, mitochondrial morphology imaging Journal of cell science Medium 34870686
2023 MARCH5 interacts with the NACHT domain of NLRP3 and promotes K27-linked polyubiquitination at K324 and K430 of NLRP3; this ubiquitination is required for NLRP3-NEK7 complex formation and NLRP3 oligomerization; myeloid-cell-specific March5 conditional knockout mice fail to secrete IL-1β/IL-18 and show attenuated LPS/P. aeruginosa-induced mortality. Co-immunoprecipitation, K27-linkage-specific ubiquitination assay, site-specific NLRP3 mutants (K324R, K430R), March5 conditional KO mice, inflammasome activation assays (IL-1β/IL-18), ASC speck formation The EMBO journal High 37575012
2023 PD-1 ligation induces BATF-dependent transcriptional upregulation of MARCH5, which then mediates K27-linked polyubiquitination and lysosomal degradation of the common cytokine receptor γ chain (γc), impairing γc family cytokine signaling in CD8+ T cells. PD-1 ligation, BATF knockout, MARCH5 overexpression/knockdown, K27-ubiquitin assay, γc protein stability measurement, cytokine signaling assays Cell research High 37932447
2023 MARCH5 ubiquitinates STING to enhance its activation; long-term MARCH5 deficiency leads to ROS production that oxidizes STING at C205, forming inactive STING polymers; MARCH5-mediated ubiquitination of STING prevents oxidation-induced inactive polymer formation. MARCH5 knockout, STING ubiquitination assay, STING polymer analysis, ROS measurement, cysteine mutant (C205) analysis EMBO reports Medium 37916870
2023 MARCH5 binds active DNA-PKcs in cells with mitochondrial DNA double-strand breaks and promotes degradation of DNA-PKcs to reduce type I interferon response; MARCH5 knockout prolongs phospho-HSPA8 levels and mIFNB1 synthesis after LPS stimulation; DNA-PKcs activation is VDAC1-dependent. Co-immunoprecipitation, MARCH5 KO macrophages, DNA-PKcs stability assay, IFN-β measurement, mtDNA DSB induction system, VDAC1-dependency analysis Cell death & disease Medium 38040710
2023 MITOL/MARCH5 ubiquitylates RECQL4 at K1101 and K1154 via K6-linked ubiquitin, preventing RECQL4 interaction with Tom20 and its mitochondrial entry; RTS patient RECQL4 mutants are hyperubiquitylated by MITOL and cannot enter mitochondria; MITOL depletion rescues mtDNA replication in some RTS mutant cells; RECQL4 accumulation on mitochondrial outer surface potentiates mitophagy. Co-immunoprecipitation, in vitro ubiquitination assay, K6-linkage ubiquitin assay, K1101/K1154 site-specific mutants, Tom20 binding assay, mitochondrial import assay, BrdU-mtDNA replication, RTS patient mutants The Journal of biological chemistry High 37495109
2023 MARCH5 mediates K48-linked ubiquitination of MIC60 at K285, promoting its degradation; mutation of MIC60 K285 or MARCH5 MIC60-interacting motifs abrogates ubiquitination; TRAP1 inhibits MARCH5-mediated MIC60 ubiquitination by competing with MARCH5 for MIC60 binding. Co-immunoprecipitation, K48-linkage ubiquitination assay, K285 site-specific mutant, MARCH5 interaction motif mutants, TRAP1 competition assay, MARCH5 silencing Cell death and differentiation High 37679468
2024 MARCH5 is essential for de novo peroxisome biogenesis from mitochondria; MARCH5 knockout leads to accumulation of immature peroxisomes and reduced peroxisomal proteins; MARCH5 redistributes to peroxisomes during fatty-acid-induced biogenesis; MARCH5 activity-deficient mutants accumulate on Tom20-positive mitochondria-derived pre-peroxisomes; MARCH5 acts upstream of Pex14 in mitochondrial steps of peroxisome biogenesis. MARCH5 knockout, double knockout (MARCH5/Pex14, MARCH5/Pex3), subcellular imaging and fractionation, fatty-acid-induced biogenesis assay, MARCH5 activity mutants Developmental cell High 39423819 39423820
2024 MARCH5 ubiquitinates and degrades MPC1 (mitochondrial pyruvate carrier 1), promoting aerobic glycolysis (Warburg effect) in ovarian cancer cells. Co-immunoprecipitation, ubiquitination assay, MPC1 stability measurement, MARCH5 knockdown/overexpression, metabolic (OCR/ECAR) assays Apoptosis Medium 38615083
2024 MARCH5 interacts with and ubiquitinates RACGAP1, promoting its degradation; MARCH5-RACGAP1-DRP1 axis controls mitochondrial quality and aortic valve calcification; inhibiting RACGAP1 reverses osteogenic transformation induced by MARCH5 silencing. Co-immunoprecipitation, mass spectrometry, molecular docking, ubiquitination assay, MARCH5 silencing/overexpression, RACGAP1 knockdown, in vivo aortic valve model Biochimica et biophysica acta. Molecular cell research Medium 39880131
2025 MARCH5 directly interacts with and ubiquitinates Trim28, targeting it for degradation; MARCH5-mediated Trim28 degradation prevents Trim28-mediated Kindlin-2 degradation, elevating MafA and insulin expression in β-cells; Trim28 deletion in β-cells rescues glucose intolerance in March5-deficient mice, establishing a March5/Trim28/Kindlin-2/MafA pathway in β-cell function. Co-immunoprecipitation, ubiquitination assay, March5 conditional β-cell KO mice, Trim28 β-cell KO mice, insulin expression and glucose tolerance assays, islet transplantation Nature communications High 40750777
2025 MARCH5 directly interacts with Akt and enhances phosphorylation of Akt, mTOR, and Gsk3β, increasing GATA4 expression and promoting cardiac hypertrophy; MARCH5 heterozygous mice subjected to TAC show attenuated cardiac hypertrophy. Co-immunoprecipitation, western blot for phosphorylation, MARCH5 overexpression/knockdown, MARCH5+/- mice with TAC model, cardiomyocyte area measurement Journal of cellular and molecular medicine Medium 40753540
2025 MARCH5 mediates K27-linked ubiquitination of JEV envelope (E) protein at K136 and K166, enhancing viral attachment; K136R-K166R double mutation attenuates JEV infection in vitro and in vivo; MARCH5 also degrades MAVS via K48-linked ubiquitination at K286, suppressing type I IFN production during JEV infection. Co-immunoprecipitation, in vivo ubiquitination assay with site-specific mutants, viral attachment assay, JEV replication assay, MARCH5 knockout, IFN measurement, in vivo mouse virulence model mBio High 40071916
2025 MARCH5 directly interacts with MIEF2 (mitochondrial fission factor) to mediate its ubiquitination and proteasomal degradation; MARCH5 overexpression reduces MIEF2 levels and reduces mitochondrial fission and fatty acid synthesis in alcoholic liver disease models; liver-specific MARCH5 knockdown worsens liver injury and abolishes gigantol-mediated protection. Co-immunoprecipitation, ubiquitination assay, MARCH5/MIEF2 overexpression/knockdown, liver-specific KD mice, mitochondrial dynamics and metabolic assays Phytomedicine Medium 41353882
2026 MITOL/MARCH5 ubiquitinates Parkin at K220 downstream of DAPK1-mediated Parkin phosphorylation (at S136 and S198); DAPK1 phosphorylation promotes mitochondrial transport of Parkin, enhancing its interaction with MITOL and leading to Parkin degradation, increasing neuronal vulnerability. Co-immunoprecipitation, phosphorylation-site mutants (S136A, S198A), ubiquitination assay, MITOL interaction assay, 6-OHDA neurotoxicity model Journal of cellular and molecular medicine Medium 41943176
2026 MARCH5 interacts with peroxisome biogenesis factor Pex26, facilitating transfer of newly synthesized Pex26 from the OMM to peroxisomes in peroxisome-containing cells; in peroxisome-deficient cells, MARCH5 targets Pex26 for p97-dependent proteasomal degradation via ubiquitination; Pex26 knockout causes accumulation of MARCH5/Tom20-positive pre-peroxisomes absent in Pex26/MARCH5 double KO cells. Co-immunoprecipitation, ubiquitination assay, Pex26 knockout, double knockout (Pex26/MARCH5), subcellular imaging, p97-dependency assay bioRxivpreprint Medium 42182360

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. The Journal of cell biology 397 17606867
2006 MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO reports 354 16936636
2017 Mitochondrial E3 ligase MARCH5 regulates FUNDC1 to fine-tune hypoxic mitophagy. EMBO reports 261 28104734
2013 MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. Molecular cell 254 23727017
2010 Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1. Journal of cell science 203 20103533
2015 The mitochondrial ubiquitin ligase MARCH5 resolves MAVS aggregates during antiviral signalling. Nature communications 141 26246171
2015 Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein. Molecular biology of the cell 127 26564796
2009 Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation. Molecular biology of the cell 115 19741096
2014 MARCH5-mediated quality control on acetylated Mfn1 facilitates mitochondrial homeostasis and cell survival. Cell death & disease 112 24722297
2019 MITOL prevents ER stress-induced apoptosis by IRE1α ubiquitylation at ER-mitochondria contact sites. The EMBO journal 101 31368599
2019 Parkin recruitment to impaired mitochondria for nonselective ubiquitylation is facilitated by MITOL. The Journal of biological chemistry 99 31110043
2016 Novel regulatory roles of Mff and Drp1 in E3 ubiquitin ligase MARCH5-dependent degradation of MiD49 and Mcl1 and control of mitochondrial dynamics. Molecular biology of the cell 79 27932492
2016 MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells. Autophagy 70 27875077
2014 Roles of mitochondrial ubiquitin ligase MITOL/MARCH5 in mitochondrial dynamics and diseases. Journal of biochemistry 64 24616159
2010 A mitochondrial ubiquitin ligase MITOL controls cell toxicity of polyglutamine-expanded protein. Mitochondrion 64 20851218
2017 MARCH5-FUNDC1 axis fine-tunes hypoxia-induced mitophagy. Autophagy 59 28486049
2011 Mitochondrial ubiquitin ligase MARCH5 promotes TLR7 signaling by attenuating TANK action. PLoS pathogens 59 21625535
2021 MITOL/MARCH5 determines the susceptibility of cardiomyocytes to doxorubicin-induced ferroptosis by regulating GSH homeostasis. Journal of molecular and cellular cardiology 57 34390730
2021 Ubiquitin ligase MARCH5 localizes to peroxisomes to regulate pexophagy. The Journal of cell biology 57 34747980
2012 Mitofusin 1 is degraded at G2/M phase through ubiquitylation by MARCH5. Cell division 57 23253261
2012 Mitochondrial ubiquitin ligase MITOL blocks S-nitrosylated MAP1B-light chain 1-mediated mitochondrial dysfunction and neuronal cell death. Proceedings of the National Academy of Sciences of the United States of America 54 22308378
2020 MARCH5 mediates NOXA-dependent MCL1 degradation driven by kinase inhibitors and integrated stress response activation. eLife 49 32484436
2019 Mitochondria ubiquitin ligase, MARCH5 resolves hepatitis B virus X protein aggregates in the liver pathogenesis. Cell death & disease 49 31819032
2023 MARCH5-dependent NLRP3 ubiquitination is required for mitochondrial NLRP3-NEK7 complex formation and NLRP3 inflammasome activation. The EMBO journal 40 37575012
2020 MARCH5-dependent degradation of MCL1/NOXA complexes defines susceptibility to antimitotic drug treatment. Cell death and differentiation 40 32015503
2020 Chaperone-mediated autophagy controls the turnover of E3 ubiquitin ligase MARCHF5 and regulates mitochondrial dynamics. Autophagy 39 33970775
2019 Baicalein inhibits mitochondrial apoptosis induced by oxidative stress in cardiomyocytes by stabilizing MARCH5 expression. Journal of cellular and molecular medicine 38 31880404
2021 The XBP1‒MARCH5‒MFN2 Axis Confers Endoplasmic Reticulum Stress Resistance by Coordinating Mitochondrial Fission and Mitophagy in Melanoma. The Journal of investigative dermatology 37 34048729
2017 PKACs attenuate innate antiviral response by phosphorylating VISA and priming it for MARCH5-mediated degradation. PLoS pathogens 37 28934360
2020 MARCH5 requires MTCH2 to coordinate proteasomal turnover of the MCL1:NOXA complex. Cell death and differentiation 36 32094511
2019 Dual targeting of RIG-I and MAVS by MARCH5 mitochondria ubiquitin ligase in innate immunity. Cellular signalling 36 31881323
2021 MITOL promotes cell survival by degrading Parkin during mitophagy. EMBO reports 35 33565245
2015 Mitochondrial E3 ligase March5 maintains stemness of mouse ES cells via suppression of ERK signalling. Nature communications 35 26033541
2016 Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA. Oncotarget 33 26910119
2023 PD-1 signaling negatively regulates the common cytokine receptor γ chain via MARCH5-mediated ubiquitination and degradation to suppress anti-tumor immunity. Cell research 32 37932447
2024 Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 38171238
2012 Inactivation of MARCH5 prevents mitochondrial fragmentation and interferes with cell death in a neuronal cell model. PloS one 27 23285122
2015 Self-clearance mechanism of mitochondrial E3 ligase MARCH5 contributes to mitochondria quality control. The FEBS journal 25 26476016
2022 MITOL-mediated DRP1 ubiquitylation and degradation promotes mitochondrial hyperfusion in a CMT2A-linked MFN2 mutant. Journal of cell science 23 34870686
2018 The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes. American journal of physiology. Endocrinology and metabolism 21 30512991
2023 TRAP1 inhibits MARCH5-mediated MIC60 degradation to alleviate mitochondrial dysfunction and apoptosis of cardiomyocytes under diabetic conditions. Cell death and differentiation 17 37679468
2021 MITOL-dependent ubiquitylation negatively regulates the entry of PolγA into mitochondria. PLoS biology 17 33657094
2011 MARCH5 gene is duplicated in rainbow trout, but only fish-specific gene copy is up-regulated after VHSV infection. Fish & shellfish immunology 17 21939770
2022 Protective roles of MITOL against myocardial senescence and ischemic injury partly via Drp1 regulation. iScience 15 35789860
2022 Mitochondrial E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins. Cell death and differentiation 15 36171332
2024 Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis. Developmental cell 14 39423819
2023 MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING. EMBO reports 12 37916870
2022 MITOL regulates phosphatidic acid-binding activity of RMDN3/PTPIP51. Journal of biochemistry 12 34964862
2021 MARCH5 restores endothelial cell function against ischaemic/hypoxia injury via Akt/eNOS pathway. Journal of cellular and molecular medicine 12 33611830
2024 Ubiquitin ligase MARCH5 controls the formation of mitochondria-derived pre-peroxisomes. Developmental cell 11 39423820
2022 MARCH5 regulates mitotic apoptosis through MCL1-dependent and independent mechanisms. Cell death and differentiation 11 36329234
2013 MARCH5 inactivation supports mitochondrial function during neurodegenerative stress. Frontiers in cellular neuroscience 10 24133412
2025 E3 ubiquitin ligase MARCH5 positively regulates Japanese encephalitis virus infection by catalyzing the K27-linked polyubiquitination of viral E protein and inhibiting MAVS-mediated type I interferon production. mBio 9 40071916
2022 Ubiquitin-mediated mitochondrial regulation by MITOL/MARCHF5 at a glance. Journal of biochemistry 8 36346121
2024 MARCH5 promotes aerobic glycolysis to facilitate ovarian cancer progression via ubiquitinating MPC1. Apoptosis : an international journal on programmed cell death 7 38615083
2023 Mitochondrial E3 ubiquitin ligase MARCH5 is required for mouse oocyte meiotic maturation†. Biology of reproduction 7 36503987
2020 march5 Governs the Convergence and Extension Movement for Organization of the Telencephalon and Diencephalon in Zebrafish Embryos. Molecules and cells 6 31910335
2019 miR-373 inhibits nasopharyngeal carcinoma cell migration and invasion by targeting MARCH5. International journal of clinical and experimental pathology 6 31934093
2023 Hyperubiquitylation of DNA helicase RECQL4 by E3 ligase MITOL prevents mitochondrial entry and potentiates mitophagy. The Journal of biological chemistry 5 37495109
2023 Mitochondrial E3 ligase MARCH5 is a safeguard against DNA-PKcs-mediated immune signaling in mitochondria-damaged cells. Cell death & disease 5 38040710
2025 Targeting the MARCH5-MFN2 axis to enhance mitochondrial fusion and sensitize multiple myeloma cells to venetoclax. Journal of translational medicine 4 40814067
2022 Protocol to detect in vitro and in cell ubiquitylation of mitochondrial DNA polymerase gamma by mitochondrial E3 ligase MITOL. STAR protocols 4 36136752
2025 Inhibiting MARCH5/Mfn2 signaling as an alternative strategy to protect cardiomyocytes from hypoxia-induced mitochondrial dysfunction. Computational and structural biotechnology journal 3 40687994
2025 METTL14-mediated lncRNA NEAT1 promotes asthma progression by regulating the miR-302a-3p/March5 axis. International immunopharmacology 2 40359886
2024 MITOL deficiency triggers hematopoietic stem cell apoptosis via ER stress response. The EMBO journal 2 38238476
2024 Molecular depiction and functional delineation of E3 ubiquitin ligase MARCH5 in yellowtail clownfish (Amphiprion clarkii). Developmental and comparative immunology 2 39481581
2024 MARCH5 Promotes the Progression of Thyroid cancer by Regulating Mitochondrial Autophagy Protein FUNDC1-mediated Pyroptosis. Applied biochemistry and biotechnology 2 39666231
2023 Outer mitochondrial membrane E3 Ub ligase MARCH5 controls mitochondrial steps in peroxisome biogenesis. bioRxiv : the preprint server for biology 2 37693581
2020 MITOL dysfunction causes dwarfism with anterior pituitary hypoplasia. Journal of biochemistry 2 32302394
2025 March5-mediated Trim28 degradation preserves islet β-cell function in mice. Nature communications 1 40750777
2025 MARCH5 Promotes Cardiac Hypertrophy by Regulating Akt/mTOR/Gsk-3β/GATA4 Signalling Pathway. Journal of cellular and molecular medicine 1 40753540
2024 MARCH5 promotes hepatocellular carcinoma progression by inducing p53 ubiquitination degradation. Journal of cancer research and clinical oncology 1 38861187
2024 Deciphering MARCH5's impact on multiple myeloma: insights into autophagy regulation and AKT-FOXO3 signaling. Blood neoplasia 1 40552133
2026 DAPK1-Mediated Parkin Inactivation Enhances Neurotoxicity via MITOL-Dependent Degradation. Journal of cellular and molecular medicine 0 41943176
2026 Inhibition of NCOA4-mediated ferritinophagy improves cardiac remodeling in diabetic cardiomyopathy via MITOL/parkin signaling. Molecular and cellular biochemistry 0 41964750
2026 Equine arteritis virus Nsp10 promotes MAVS proteasomal degradation via E3 ligases Smurf1/MARCH5. Journal of virology 0 42153738
2026 Dual role of the OMM E3 Ub ligase MARCH5 in de novo peroxisome biogenesis and mitochondrial quality control through direct regulation of Pex26. bioRxiv : the preprint server for biology 0 42182360
2025 MARCH5 ameliorates aortic valve calcification via RACGAP1-DRP1 associated mitochondrial quality control. Biochimica et biophysica acta. Molecular cell research 0 39880131
2025 MARCH5-mediated MIEF2 ubiquitination and degradation contribute to gigantol to against hepatic steatosis and mitochondrial fission in alcoholic liver disease. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41353882
2024 The Mitochondrial Ubiquitin Ligase MARCHF5 Cooperates with MCL1 to Inhibit Apoptosis in KSHV-Transformed Primary Effusion Lymphoma Cell Lines. bioRxiv : the preprint server for biology 0 39386614
2021 The ides of MARCH5: The E3 ligase essential for peroxisome degradation by pexophagy. The Journal of cell biology 0 34889952

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