Affinage

MFF

Mitochondrial fission factor · UniProt Q9GZY8

Length
342 aa
Mass
38.5 kDa
Annotated
2026-04-28
79 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MFF is a tail-anchored outer mitochondrial membrane protein that functions as the primary receptor for recruiting higher-order Drp1 oligomers to drive mitochondrial and peroxisomal fission, with its activity amplified by actin filaments and dependent on its own oligomerization through a C-terminal coiled coil (PMID:18353969, PMID:21149567, PMID:34347505). MFF activity is regulated by a convergence of post-translational modifications: AMPK, PKD, JNK/CK2α-mediated phosphorylation promotes Drp1 recruitment and fission; SUMOylation at Lys151 controls MiD49/51 binding within trimeric fission complexes; succinylation at Lys302 protects MFF from Parkin-mediated degradation; and ubiquitination by Parkin or TRIM21 directs its constitutive turnover (PMID:39365854, PMID:34010649, PMID:37291333, PMID:31112535, PMID:41650744). Beyond organelle division, MFF independently promotes active MAVS cluster formation on the mitochondrial surface for innate antiviral signaling, forms complexes with VDAC1 to regulate outer membrane permeability, and mediates ARP2/3-dependent actin-based melanosome fission (PMID:33177519, PMID:31582380, PMID:41832149). In neurons, local MFF translation at mitochondrial fission sites is spatially controlled by FMRP-containing RNA granules, and Mff-deficient mice develop fatal dilated cardiomyopathy rescued by concomitant loss of the fusion factor Mfn1 (PMID:39548330, PMID:26598616).

Mechanistic history

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

    MFF was identified as a novel mitochondrial fission factor, resolving the question of whether mammalian fission required additional receptors beyond Fis1: MFF knockdown phenocopied Drp1 loss, establishing it as a core fission component.

    Evidence siRNA knockdown with subcellular fractionation, gel filtration, and fluorescence microscopy in mammalian cells

    PMID:18353969

    Open questions at the time
    • Direct physical interaction with Drp1 not yet demonstrated
    • Mechanism of MFF action at the membrane unknown
  2. 2010 High

    The key question of whether MFF directly recruits Drp1 was answered: MFF physically binds Drp1 in vitro and in vivo, and plasma membrane-retargeted MFF redirects Drp1, establishing MFF as a bona fide Drp1 receptor independent of Fis1.

    Evidence Reciprocal co-IP, in vitro pulldown, CAAX plasma membrane targeting, gain/loss-of-function

    PMID:21149567

    Open questions at the time
    • Structural basis of MFF-Drp1 interaction unresolved
    • Whether MFF distinguishes Drp1 oligomeric states unknown
  3. 2013 High

    The question of receptor redundancy was addressed: MiD49/51 can independently recruit Drp1 in Mff-null/Fis1-null cells, and MFF also functions in peroxisomal fission by recruiting Drp1 to peroxisomes in cooperation with Pex11pβ.

    Evidence Fis1-null, Mff-null, and double-null cell lines; Drp1 puncta quantification; co-IP of MFF-Pex11pβ

    PMID:23283981 PMID:24167709

    Open questions at the time
    • Relative contributions of MFF versus MiD49/51 in different tissues unclear
    • Pex11pβ-MFF interaction not reconstituted in vitro
  4. 2015 High

    Multiple advances resolved how MFF selectivity, regulation, and physiological importance operate: MFF selectively binds higher-order Drp1 oligomers (unlike MiD49/51 which recruit dimers), Drp1 Ser637 dephosphorylation enhances MFF binding, Parkin ubiquitinates MFF at Lys251 to link it to mitophagy, and Mff-knockout mice develop fatal dilated cardiomyopathy rescued by concomitant Mfn1 deletion.

    Evidence Recombinant protein binding with assembly mutants; phosphomimetic/phospho-deficient Drp1 mutants and co-IP; ubiquitination assay with K251R mutant; Mff-null and Mff/Mfn1 double-knockout mice with cardiac phenotyping

    PMID:26008206 PMID:26432782 PMID:26446846 PMID:26598616

    Open questions at the time
    • Structural basis of oligomer selectivity not defined
    • Identity of kinase/phosphatase for Drp1 Ser637 in this context not fully resolved
    • Whether additional E3 ligases ubiquitinate MFF unknown
  5. 2016 High

    MFF was placed within a broader regulatory network: MiD51 suppresses MFF-dependent Drp1 GTPase activation, and MFF/Drp1 negatively regulate MARCH5 E3 ligase activity toward OMM substrates including MiD49 and Mcl1.

    Evidence BioID proximity labeling, CRISPR knockouts, Drp1 GTPase assay; multiple KO combinations with ubiquitination and stability assays

    PMID:27076521 PMID:27932492

    Open questions at the time
    • How MFF inhibits MARCH5 mechanistically is unclear
    • Whether MiD51-MFF interplay is tissue-specific not tested
  6. 2017 High

    Post-translational control of the MFF-Drp1 axis was expanded: SENP3-mediated deSUMOylation of Drp1 selectively promotes Drp1 binding to MFF, and JNK-mediated MFF phosphorylation/upregulation drives pathological fission counteracted by DUSP1.

    Evidence SUMO site mutants with co-IP; SENP3 knockdown/overexpression; transgenic mouse cardiac ischemia-reperfusion model with DUSP1

    PMID:28262828 PMID:29149759

    Open questions at the time
    • Direct phosphorylation sites on MFF by JNK not mapped
    • Whether SENP3-Drp1-MFF axis operates in all tissues unknown
  7. 2018 High

    MFF was shown to function beyond simple fission: it forms complexes with VDAC1 to regulate mitochondrial outer membrane permeability, controls neuronal mitochondrial size and presynaptic calcium/neurotransmitter release, and CK2α was identified as an upstream kinase phosphorylating MFF during cardiac ischemia.

    Evidence MFF-VDAC1 co-IP with mutagenesis and peptidomimetic disruption; in utero electroporation with shRNA and Ca2+ imaging in neurons; NR4A1 KO mice with CK2α inhibition

    PMID:29744594 PMID:30479337 PMID:31582380

    Open questions at the time
    • Structural detail of MFF-VDAC1 complex lacking
    • Whether MFF-VDAC1 interaction is relevant to non-tumor physiology untested
    • Specific phosphorylation sites for CK2α on MFF not mapped
  8. 2020 High

    An entirely fission-independent function was established: MFF promotes active MAVS cluster formation on mitochondria for antiviral signaling, and AMPK phosphorylation of MFF under metabolic stress disorganizes MAVS clusters to suppress innate immunity.

    Evidence Mff knockout cells, AMPK phosphorylation assay, MAVS oligomerization and innate immune reporter assays

    PMID:33177519

    Open questions at the time
    • Structural basis of MFF-MAVS interaction unknown
    • Whether MFF organizes other signaling platforms not explored
  9. 2021 High

    The biophysical mechanism of MFF was resolved: MFF is an oligomer (likely trimer) whose dynamic self-assembly through its coiled coil is essential for Drp1 activation, and actin filaments enhance this by lowering the effective MFF concentration ~10-fold; separately, PKD was identified as the mitosis-specific MFF kinase required for chromosome segregation.

    Evidence In vitro reconstitution with purified proteins, TIRF microscopy, GTPase assay, Mff-KO rescue with oligomerization-defective mutants; in vitro kinase assay with phospho-mutant rescue and chromosome segregation assays

    PMID:34010649 PMID:34347505

    Open questions at the time
    • Atomic structure of MFF oligomer not determined
    • How actin filaments are positioned at fission sites relative to MFF in vivo unclear
    • Whether PKD phosphorylation affects MFF oligomerization untested
  10. 2023 Medium

    A novel stabilizing modification was identified: CPT1A-mediated succinylation of MFF at Lys302 protects MFF from Parkin-mediated ubiquitin-proteasomal degradation, linking metabolic rewiring to fission control in cancer.

    Evidence Mass spectrometry identification of succinylation site, K302R mutagenesis, ubiquitination assay, in vivo xenograft

    PMID:37291333

    Open questions at the time
    • Whether succinylation-ubiquitination crosstalk on MFF operates in non-cancer contexts unknown
    • Desuccinylase for Lys302 not identified
  11. 2024 High

    Two regulatory layers were defined: AMPK-dependent phosphorylation enhances MFF SUMOylation at Lys151, which controls MiD49/51 binding within trimeric DRP1-MiD-MFF complexes; and FMRP granules control local MFF translation at mitochondrial fission sites in neurons to spatially regulate replicative versus peripheral fission.

    Evidence SUMO site ID with K151R rescue in MFF-KO MEFs; cryo-ET, real-time SunTag translation imaging, FMRP conditional KO in neurons; isoform rescue with splice variants in KO MEFs

    PMID:39293584 PMID:39365854 PMID:39548330

    Open questions at the time
    • How SUMOylation structurally alters MFF-MiD binding not resolved
    • Whether FMRP-dependent local translation of MFF occurs outside neurons unknown
    • Functional significance of most MFF splice isoforms untested in vivo
  12. 2025 Medium

    An additional E3 ubiquitin ligase, TRIM21, was identified as mediating MFF degradation, linking MFF turnover to trophoblast senescence and miscarriage; separately, MFF was shown to traffic to melanosomes and drive actin/ARP2/3-dependent melanosome fission independent of Drp1.

    Evidence TRIM21 co-IP and ubiquitination assay with in vivo mouse model; MFF knockdown with live imaging, ARP2/3 subunit knockdown, and melanosome morphology in melanocytes

    PMID:41650744 PMID:41832149

    Open questions at the time
    • TRIM21-MFF ubiquitination sites not mapped
    • Whether MFF-ARP2/3 interaction is direct or mediated by adaptors unclear
    • Mechanism of MFF trafficking from mitochondria to melanosomes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of MFF (as monomer and oligomer), the structural basis of its selective recognition of higher-order Drp1 oligomers, how MFF coordinates its dual fission-dependent and fission-independent functions (MAVS signaling, VDAC1 regulation, melanosome fission), and the full landscape of tissue-specific splice isoform functions in vivo.
  • No high-resolution structure of MFF available
  • Mechanism of MFF trafficking between organelles unknown
  • Relative in vivo contributions of multiple MFF kinases and E3 ligases not systematically compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 5 GO:0005777 peroxisome 2 GO:0005886 plasma membrane 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1
Partners
DNM1LMAVSMIEF1MIEF2PRKAA1PRKD1PRKNVDAC1
Complex memberships
DRP1-MFF fission complexDRP1-MiD49/51-MFF trimeric complexMFF-VDAC1 complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MFF is a tail-anchored mitochondrial outer membrane protein that controls mitochondrial fission; it exists in separate ~200 kDa complexes from Fis1, and siRNA knockdown phenocopies Drp1 and Fis1 loss, causing mitochondrial network formation, delay in cytochrome c release, and inhibition of peroxisomal fission. siRNA knockdown, subcellular fractionation, gel filtration, fluorescence microscopy, apoptosis assays Molecular biology of the cell High 18353969
2010 Mff is an essential receptor for Drp1 recruitment to the mitochondrial outer membrane; Mff and Drp1 physically interact in vitro and in vivo (co-IP, pulldown), Mff knockdown releases Drp1 foci from mitochondria, and Mff overexpression drives mitochondrial fission independent of Fis1. A plasma membrane-targeted Mff mutant (CAAX) redirects Drp1 to the plasma membrane. Knockdown/overexpression, co-immunoprecipitation, in vitro pulldown, CAAX targeting assay, fluorescence microscopy The Journal of cell biology High 21149567
2013 Fis1 and Mff both contribute to Drp1 recruitment and mitochondrial fission; Fis1-null and Mff-null cells show reduced Drp1 puncta on mitochondria, and MiD49 or MiD51 can each independently recruit Drp1 and mediate fission in the absence of both Fis1 and Mff. Gene knockout (Fis1-null, Mff-null, double null), immunofluorescence, Drp1 puncta quantification Molecular biology of the cell High 23283981
2013 Mff functions in peroxisomal fission by localizing to peroxisomal membrane-constricted regions and recruiting DLP1 (Drp1) to peroxisomes; Mff knockdown abrogates DLP1 recruitment to peroxisomes. Mff and Pex11pβ interact in a DLP1-dependent manner to co-regulate peroxisomal fission. siRNA knockdown, immunofluorescence localization, co-immunoprecipitation, overexpression Biology open Medium 24167709
2015 Mff selectively recruits higher-order oligomers of Drp1: assembly-deficient Drp1 mutants cannot bind Mff, whereas Drp1 mutants lacking the insert B region (which normally inhibits Mff-Drp1 interaction) form stable complexes with Mff. In contrast, MiD49/51 can recruit Drp1 dimers. Genetic and biochemical assays, recombinant protein binding, Drp1 assembly mutants Molecular biology of the cell High 26446846
2015 Mff-deficient mice develop fatal dilated cardiomyopathy with reduced mitochondrial density, impaired respiratory chain activity, and increased mitophagy; concomitant deletion of the fusion gene Mfn1 completely rescues cardiac function and lifespan, demonstrating that Mff-dependent fission must be balanced against fusion for tissue integrity. Mouse knockout (Mff-null, Mff/Mfn1 double knockout), cardiac function assays, electron microscopy, metabolomics The Journal of cell biology High 26598616
2015 The phosphorylation status of Drp1 at Ser637 is essential for its interaction with Mff; UV irradiation decreases Drp1-Ser637 phosphorylation and enhances Drp1-Mff interaction, driving mitochondrial fragmentation. Mff-mediated Drp1 recruitment does not require Bax. Co-immunoprecipitation, phosphomimetic/phospho-deficient mutants, siRNA, UV apoptosis model FASEB journal Medium 26432782
2015 Parkin mediates poly-ubiquitination of Mff at Lys251 upon mitochondrial depolarization; ubiquitinated Mff promotes association with the autophagic adaptor p62/SQSTM1, and Mff knockout impairs p62 and Parkin translocation to damaged mitochondria, linking Mff to mitophagy. Co-immunoprecipitation, ubiquitination assay, K251R point mutant, Mff knockout, fluorescence microscopy Acta biochimica et biophysica Sinica Medium 26008206
2016 Mff and Drp1 are components of the MARCH5/p97/Npl4 ubiquitin ligase complex; Mff and Drp1 knockouts reduce expression and increase ubiquitination of MiD49 and Mcl1 in a MARCH5-dependent manner, revealing that Mff negatively regulates MARCH5 E3 ligase activity toward specific OMM substrates. Gene knockout (Drp1-/-, Mff-/-, double KO with MARCH5-/-), co-immunoprecipitation, ubiquitination assay, protein stability assay Molecular biology of the cell Medium 27932492
2016 MiD51 suppresses Mff-dependent enhancement of Drp1 GTPase activity; proximity biotin labeling shows close association between MiD51, Mff and Drp1, but not Fis1; and combined loss of MiD51 and Mff causes greater mitochondrial connectivity than loss of either alone. BioID proximity labeling, CRISPR/Cas9 knockout cell lines, Drp1 GTPase activity assay, electron microscopy Journal of cell science High 27076521
2017 JNK pathway activation upregulates Mff expression/phosphorylation; elevated Mff drives excessive mitochondrial fission leading to mitochondrial apoptosis; DUSP1 (a JNK phosphatase) suppresses this pathway, and DUSP1 overexpression reduces Mff-mediated fission and protects against cardiac ischemia-reperfusion injury. Transgenic mouse model, siRNA knockdown, Western blot, mitochondrial morphology assay, apoptosis assay Redox biology Medium 29149759
2017 SENP3-mediated deSUMOylation of Drp1 selectively promotes Drp1 binding to Mff on the mitochondrial outer membrane; preventing Drp1 SUMOylation by mutating SUMO acceptor sites enhances Mff binding, while increasing Drp1 SUMOylation by SENP3 knockdown reduces Mff binding and stress-induced cytochrome c release. Directly tethering Drp1 to the OMM bypasses the need for Mff. Co-immunoprecipitation, SUMOylation site mutants, SENP3 overexpression/knockdown, cytochrome c release assay Scientific reports High 28262828
2018 CK2α (casein kinase 2α), activated downstream of NR4A1 during cardiac microvascular ischemia-reperfusion, phosphorylates Mff, which enhances Drp1 translocation to mitochondria and causes fatal mitochondrial fission. NR4A1 knockout mice, CK2α inhibition, Western blot for phospho-Mff, mitochondrial morphology, apoptosis assay Basic research in cardiology Medium 29744594
2018 MFF (isoforms MFF1 and MFF2) forms homo- and heterodimeric complexes with VDAC1 (voltage-dependent anion channel 1) using Arg225, Arg236, and Gln241 as key contact sites; disrupting this complex with a cell-permeable peptidomimetic acutely depolarizes mitochondria and triggers cell death selectively in tumor cells. Co-immunoprecipitation, mass spectrometry interactome, mutagenesis (Arg225, Arg236, Gln241), peptidomimetic disruption, patient-derived xenografts Cancer research High 31582380
2018 MFF is regulated at the post-transcriptional level by the RNA-binding protein BRCA1 via transactivation of miR-593-5p, which targets the 3'UTR of MFF mRNA to suppress translation and attenuate mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma. 3'UTR luciferase reporter, miR-593-5p overexpression/knockdown, BRCA1 transactivation assay, in vivo xenograft Oncotarget Medium 25912308
2018 MFF mediates mitochondrial fission by recruiting Drp1; Mff-deficient cardiac microvascular endothelial cells show reduced mitochondrial fission and inhibited mPTP opening via blockade of VDAC1 oligomerization and prevention of hexokinase 2 dissociation from mitochondria, reducing cardiolipin oxidation and cytochrome c release. Mff-deficient (Mffgt) mice and siRNA, mPTP opening assay, VDAC1 oligomerization assay, hexokinase 2 co-IP, mitochondrial ROS and cardiolipin oxidation measurement Journal of the American Heart Association Medium 28288978
2018 MFF is required for axonal mitochondrial size maintenance in cortical neurons; MFF downregulation increases presynaptic mitochondrial size, augments mitochondrial Ca2+ uptake during neurotransmission, and reduces presynaptic Ca2+ accumulation, decreasing neurotransmitter release and terminal axon branching. In utero electroporation, shRNA knockdown, live imaging, mitochondrial Ca2+ and membrane potential measurement, presynaptic release assay Nature communications High 30479337
2019 Parkin ubiquitinates Mff in a PINK1-dependent manner under non-stressed (basal) conditions to regulate constitutive Mff turnover; at least one additional ubiquitin ligase contributes to Mff proteostasis in the absence of Parkin. shRNA knockdown of Parkin/PINK1, ubiquitination assay, protein half-life measurement PloS one Medium 31112535
2020 Mff mediates formation of active MAVS clusters on the mitochondrial outer membrane, independent of mitochondrial fission and Drp1; under mitochondrial dysfunction, AMPK phosphorylates Mff, leading to disorganization of MAVS clusters and repression of antiviral signaling. Mff knockout cells, AMPK phosphorylation assay, MAVS oligomerization assay, innate immune reporter assay, confocal imaging Nature communications High 33177519
2021 Mff is an oligomer (most likely a trimer) that dynamically associates through its C-terminal coiled coil (Kd ~10 µM); dynamic Mff oligomerization is required for Drp1 activation. Actin filaments enhance Mff-mediated Drp1 activation by lowering effective Mff concentration ~10-fold. TIRF microscopy shows Mff interacts with Drp1 on actin filaments in an oligomerization-dependent manner. In cells, oligomerization-defective Mff fails to rescue mitochondrial division, Drp1 recruitment, or peroxisome division in Mff-KO cells. In vitro reconstitution with purified proteins, GTPase activation assay, TIRF microscopy, Mff-KO rescue with oligomerization-defective mutants Molecular biology of the cell High 34347505
2021 Protein kinase D (PKD) directly phosphorylates MFF specifically during mitosis; PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic (but not interphase) cells, and this fission is critical for chromosome segregation and cell survival by inhibiting adaptation of the mitotic checkpoint. In vitro kinase assay, phospho-specific antibodies, MFF phosphorylation-deficient mutants, live imaging, chromosome segregation assay Cell reports High 34010649
2021 Mff preferentially binds higher-order Drp1 oligomers and only recruits active forms of Drp1, whereas MIEFs bind a wider range including lower oligomeric states and inactive Drp1. MIEFs serve as a platform facilitating Drp1 binding to Mff; loss of MIEFs severely impairs the Drp1-Mff interaction. In vivo chemical crosslinking, co-immunoprecipitation, assembly-deficient and GTPase-deficient Drp1 mutants, triple (Mff/MIEF1/MIEF2) knockout cells Frontiers in cell and developmental biology Medium 34805137
2021 In an OGD/ischemia model, Mff primes Drp1 binding to Bcl-xL at the mitochondrial outer membrane; Mff and Bcl-xL interact directly through their transmembrane domains independent of Drp1. SENP3-mediated Drp1 deSUMOylation promotes the Drp1-Bcl-xL interaction and ischemia-induced cell death. Co-immunoprecipitation in vivo and in vitro, OGD model, SENP3 knockdown/overexpression, Bcl-xL transmembrane mutant Frontiers in cell and developmental biology Medium 34722538
2022 HCMV vMIA inhibits MAVS oligomerization at peroxisomes in an MFF-dependent manner; vMIA interacts with MAVS at peroxisomes and requires MFF for peroxisomal fragmentation, but MFF is dispensable for vMIA-mediated inhibition of mitochondrial MAVS signaling. siRNA knockdown of MFF, MAVS oligomerization assay, immunofluorescence, co-immunoprecipitation, peroxisome morphology Frontiers in cell and developmental biology Medium 35445031
2023 CPT1A promotes succinylation of MFF at Lys302 through its lysine succinyltransferase activity; this succinylation protects MFF from Parkin-mediated ubiquitin-proteasomal degradation, stabilizing MFF to promote mitochondrial fission and ovarian cancer cell growth. Mass spectrometry, site-directed mutagenesis (K302R), co-immunoprecipitation, ubiquitination assay, in vivo xenograft Communications biology Medium 37291333
2024 FMRP granules are recruited to mitochondrial fission sites in axons and dendrites; FMRP promotes local translation of MFF at the mitochondrial midzone via ribosome-rich granules, specifically enabling replicative fission. Loss of FMRP dysregulates MFF local translation, increases peripheral fission, and disrupts mitochondrial nucleoid distribution. Cryo-electron tomography, real-time translation imaging (SunTag), FMRP conditional KO, live imaging, Rab7 GTPase manipulation Nature cell biology High 39548330
2024 MFF is SUMOylated at Lys151; AMPK-mediated phosphorylation of MFF enhances its SUMOylation. MFF SUMOylation regulates MiD49/51 binding to MFF within trimeric DRP1-MiD-MFF fission complexes, and non-SUMOylatable MFF K151R impairs CCCP-induced mitochondrial fragmentation in MFF-KO MEFs. SUMO site identification, phosphomimetic/phospho-deficient mutants, K151R non-SUMOylatable mutant rescue, MFF-KO MEFs, CCCP stress assay Science advances High 39365854
2024 Alternative splicing of Mff exon 6 insertion (just after the AMPK phosphorylation site) reduces AMPK-mediated Mff phosphorylation and impairs both mitochondrial fission and MAVS-mediated antiviral response in a phosphorylation-independent manner; tissue-specific splicing patterns regulate Mff function. Mff knockout MEFs rescued with single splice isoforms, AMPK phosphorylation assay, mitochondrial morphology, innate immune reporter assay Pharmacological research Medium 39293584
2025 TRIM21 mediates ubiquitination and proteasomal degradation of MFF; ciprofloxacin upregulates TRIM21, reducing MFF levels and causing mitochondrial dysfunction and trophoblast cell senescence leading to miscarriage. Co-immunoprecipitation, ubiquitination assay, TRIM21 knockdown/overexpression, mouse model, trophoblast cell line EBioMedicine Medium 41650744
2026 MFF traffics between mitochondria and melanosomes and localizes to melanosome fission events; MFF downregulation causes melanosome enlargement, intracellular melanin accumulation, and increased lumenal catabolism independent of Drp1. MFF interacts with regulators of the ARP2/3 complex; actin filaments accumulate at MFF-enriched membrane constriction sites between melanosomes, and silencing ARP2/3 subunits phenocopies MFF loss, revealing an extramitochondrial MFF function in actin-dependent melanosome fission. MFF knockdown, live imaging, co-immunoprecipitation with ARP2/3 regulators, actin staining, ARP2/3 subunit knockdown, melanosome morphology and melanin quantification Nature communications Medium 41832149

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Molecular biology of the cell 993 23283981
2010 Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. The Journal of cell biology 898 21149567
2008 The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Molecular biology of the cell 618 18353969
2017 DUSP1 alleviates cardiac ischemia/reperfusion injury by suppressing the Mff-required mitochondrial fission and Bnip3-related mitophagy via the JNK pathways. Redox biology 400 29149759
2017 Mff-Dependent Mitochondrial Fission Contributes to the Pathogenesis of Cardiac Microvasculature Ischemia/Reperfusion Injury via Induction of mROS-Mediated Cardiolipin Oxidation and HK2/VDAC1 Disassociation-Involved mPTP Opening. Journal of the American Heart Association 277 28288978
2018 NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2α. Basic research in cardiology 275 29744594
2016 Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. Journal of cell science 263 27076521
2013 Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. The Journal of biological chemistry 247 23921378
2018 MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. Nature communications 208 30479337
2015 The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1. Molecular biology of the cell 155 26446846
2015 Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy. The Journal of cell biology 138 26598616
2016 Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy. Journal of medical genetics 101 26783368
2015 Drp1, Mff, Fis1, and MiD51 are coordinated to mediate mitochondrial fission during UV irradiation-induced apoptosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 98 26432782
2018 Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway. Cell death & disease 94 29725013
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 78 27932492
2018 DUSP1 recuses diabetic nephropathy via repressing JNK-Mff-mitochondrial fission pathways. Journal of cellular physiology 70 30191967
2020 Pum2-Mff axis fine-tunes mitochondrial quality control in acute ischemic kidney injury. Cell biology and toxicology 69 31993882
2017 SENP3-mediated deSUMOylation of Drp1 facilitates interaction with Mff to promote cell death. Scientific reports 62 28262828
2013 Mff functions with Pex11pβ and DLP1 in peroxisomal fission. Biology open 56 24167709
2018 NR4A1 Promotes Diabetic Nephropathy by Activating Mff-Mediated Mitochondrial Fission and Suppressing Parkin-Mediated Mitophagy. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 55 30077998
2020 MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity. Nature communications 49 33177519
2020 Drp1/Mff signaling pathway is involved in fluoride-induced abnormal fission of hepatocyte mitochondria in mice. The Science of the total environment 48 32278173
2019 MFF Regulation of Mitochondrial Cell Death Is a Therapeutic Target in Cancer. Cancer research 47 31582380
2015 Mitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1-miR-593-5p-MFF axis. Oncotarget 46 25912308
2022 Regulator of calcineurin 1 deletion attenuates mitochondrial dysfunction and apoptosis in acute kidney injury through JNK/Mff signaling pathway. Cell death & disease 42 36071051
2018 Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK-Mff signaling pathways. BMC cell biology 41 30253740
2018 LATS2 promotes apoptosis in non-small cell lung cancer A549 cells via triggering Mff-dependent mitochondrial fission and activating the JNK signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 39 30551520
2023 Carnitine palmitoyltransferase 1A promotes mitochondrial fission by enhancing MFF succinylation in ovarian cancer. Communications biology 36 37291333
2021 Mff oligomerization is required for Drp1 activation and synergy with actin filaments during mitochondrial division. Molecular biology of the cell 36 34347505
2020 Mitochondrial Fission Factor (MFF) Inhibits Mitochondrial Metabolism and Reduces Breast Cancer Stem Cell (CSC) Activity. Frontiers in oncology 36 33194575
2012 TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression. PloS one 35 23284813
2024 FMRP regulates MFF translation to locally direct mitochondrial fission in neurons. Nature cell biology 28 39548330
2022 AMPK/MFF Activation: Role in Mitochondrial Fission and Mitophagy in Dry Eye. Investigative ophthalmology & visual science 28 36374514
2021 Hypoxia-induced ROS promotes mitochondrial fission and cisplatin chemosensitivity via HIF-1α/Mff regulation in head and neck squamous cell carcinoma. Cellular oncology (Dordrecht, Netherlands) 28 34460078
2021 Melatonin Attenuates ox-LDL-Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling. Oxidative medicine and cellular longevity 26 33763168
2021 A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression. Cell reports 26 34010649
2021 The Molecular Assembly State of Drp1 Controls its Association With the Mitochondrial Recruitment Receptors Mff and MIEF1/2. Frontiers in cell and developmental biology 25 34805137
2018 Potential use of TIA-1, MFF, microRNA-200a-3p, and microRNA-27 as a novel marker for hepatocellular carcinoma. Biochemical and biophysical research communications 24 29496454
2023 Kaempferol induces mitochondrial dysfunction and mitophagy by activating the LKB1/AMPK/MFF pathway in breast precancerous lesions. Phytotherapy research : PTR 22 37086359
2015 Parkin-induced ubiquitination of Mff promotes its association with p62/SQSTM1 during mitochondrial depolarization. Acta biochimica et biophysica Sinica 21 26008206
2020 Encephalopathy due to defective mitochondrial and peroxisomal fission 2 caused by a novel MFF gene mutation in a young child. Clinical genetics 20 32181496
2025 CPT1A-mediated MFF succinylation promotes stemness maintenance in ovarian cancer stem cells. Communications biology 19 39956875
2022 The MFF-SIRT1/3 axis, regulated by miR-340-5p, restores mitochondrial homeostasis of hypoxia-induced pulmonary artery smooth muscle cells. Laboratory investigation; a journal of technical methods and pathology 19 35042949
2022 Human Cytomegalovirus vMIA Inhibits MAVS Oligomerization at Peroxisomes in an MFF-Dependent Manner. Frontiers in cell and developmental biology 16 35445031
2015 Differential autophagic effects triggered by five different vertebrate iridoviruses in a common, highly permissive mandarinfish fry (MFF-1) cell model. Fish & shellfish immunology 16 26748344
2024 SIRT1 regulates mitochondrial fission to alleviate high altitude hypoxia inducedcardiac dysfunction in rats via the PGC-1α-DRP1/FIS1/MFF pathway. Apoptosis : an international journal on programmed cell death 15 38678130
2024 DKK3 promotes renal fibrosis by increasing MFF-mediated mitochondrial dysfunction in Wnt/β-catenin pathway-dependent manner. Renal failure 13 38682264
2024 SUMOylation of MFF coordinates fission complexes to promote stress-induced mitochondrial fragmentation. Science advances 12 39365854
2023 Mdivi1 ameliorates mitochondrial dysfunction in non-alcoholic steatohepatitis by inhibiting JNK/MFF signaling. Journal of gastroenterology and hepatology 12 37839851
2019 Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff). PloS one 12 31112535
2019 Sirt1 inhibits HG-induced endothelial injury: Role of Mff-based mitochondrial fission and F‑actin homeostasis-mediated cellular migration. International journal of molecular medicine 12 31115479
2022 Mitochondrial Calcium-Triggered Oxidative Stress and Developmental Defects in Dopaminergic Neurons Differentiated from Deciduous Teeth-Derived Dental Pulp Stem Cells with MFF Insufficiency. Antioxidants (Basel, Switzerland) 11 35883852
2021 SENP3 Promotes an Mff-Primed Bcl-x -Drp1 Interaction Involved in Cell Death Following Ischemia. Frontiers in cell and developmental biology 10 34722538
2024 Alternative splicing of Mff regulates AMPK-mediated phosphorylation, mitochondrial fission and antiviral response. Pharmacological research 9 39293584
2023 Senomorphic effect of diphenyleneiodonium through AMPK/MFF/DRP1 mediated mitochondrial fission. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 7 37004322
2022 Mitochondrial fission factor (MFF) frameshift variant in Bullmastiffs with mitochondrial fission encephalopathy. Animal genetics 7 36085405
2022 iTTCA-MFF: identifying tumor T cell antigens based on multiple feature fusion. Immunogenetics 6 35246701
2020 Mcl-1 inhibits Mff-mediated mitochondrial fragmentation and apoptosis. Biochemical and biophysical research communications 5 31941601
2019 Quantifying the inhibitory effect of Bcl-xl on the action of Mff using live-cell fluorescence imaging. FEBS open bio 5 31587505
2025 The Role of Placental MFF-Mediated Mitochondrial Fission in Gestational Diabetes Mellitus. Diabetes, metabolic syndrome and obesity : targets and therapy 4 39995822
2022 Blocking exosomal secretion aggravates 1,4-benzoquinone-induced mitochondrial fission activated by the AMPK/MFF/Drp1 pathway in HL-60 cells. Journal of applied toxicology : JAT 4 35383983
2025 Scale drop disease virus (SDDV) triggers ferroptosis both in mandarin fish (Siniperca chuatsi) and MFF-1 cells to facilitate virus infection via linking to transferrin receptor 1 (TfR1). Fish & shellfish immunology 3 40373888
2024 MFF-DTA: Multi-scale feature fusion for drug-target affinity prediction. Methods (San Diego, Calif.) 3 39218169
2023 A Heterozygous Mutation in MFF Associated with a Mild Mitochondrial Phenotype. Journal of neuromuscular diseases 3 36314214
2025 MFF-nDA: A Computational Model for ncRNA-Disease Association Prediction Based on Multimodule Fusion. Journal of chemical information and modeling 2 40129032
2025 CUMS stress facilitates hippocampal neural mitophagy through FIS1/MFF-mediated mitochondrial fragmentation. Journal of neurophysiology 2 40748742
2023 Pectoralis Major Myofascial (PMMF) Flap as a Valuable Alternative to Microvascular Free Flaps (MFF) in Females with Advanced Oral Squamous Cell Carcinomas: A Retrospective Institutional Analysis. Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India 2 37974769
2025 Bacillus velezensis MFF 2.2-derived lipopeptides modulate gut immune response in BALB/c mice maintaining mucosal integrity and systemic safety. Veterinary research communications 1 40192874
2026 Targeting MFF succinylation: a novel therapeutic strategy for premature ovarian insufficiency by restoring mitochondrial dynamics in granulosa cells. Journal of ovarian research 0 41549306
2026 Environmental ciprofloxacin triggers pregnancy loss: senescence-driven miscarriage via TRIM21-mediated MFF degradation. EBioMedicine 0 41650744
2026 MFF-AE: Enhanced Quality Control for Proteomics Mass Spectrometry Data via Multi-Scale Feature Fusion. International journal of molecular sciences 0 41828350
2026 MFF budding from mitochondria regulates melanosome size and maturation. Nature communications 0 41832149
2025 MFF-HPO: Protein-Phenotype Associations Prediction Based on Sequence Using Multi-Feature Fusion. Journal of computational biology : a journal of computational molecular cell biology 0 40589089
2025 MicroRNA-27b alleviates septic cardiomyopathy by targeting the Mff/MAVS axis. Frontiers in cellular and infection microbiology 0 40766842
2025 [Effects of heat-reinforcing acupuncture on Drp1/Mff pathway activity and mitochondrial quality in rabbits with cold-dampness rheumatoid arthritis]. Zhen ci yan jiu = Acupuncture research 0 41116985
2025 Anti-inflammatory gut immune modulation induced by direct-fed endospores of bacteriostatic lipopeptide-producing Bacillus velezensis MFF 2.2 and B. subtilis TC12 in BALB/c mice: A first step toward a probiotic additive to prevent post-weaning diarrhea. Research in veterinary science 0 41447962
2024 [Retracted] Sirt1 inhibits HG‑induced endothelial injury: Role of Mff‑based mitochondrial fission and F‑actin homeostasis‑mediated cellular migration. International journal of molecular medicine 0 38940352
2024 Inhibition of mitochondrial over-division by (+)-14,15-Dehydrovincamine attenuates cisplatin-induced acute kidney injury via the JNK/Mff pathway. Free radical biology & medicine 0 39197599
2023 Bilateral plaque like macular atrophy and pigmentary retinopathy in an infant with a missense mutation in the MFF gene. Ophthalmic genetics 0 36946373