Affinage

MFF

Mitochondrial fission factor · UniProt Q9GZY8

Length
342 aa
Mass
38.5 kDa
Annotated
2026-06-10
80 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MFF is a tail-anchored protein of the mitochondrial and peroxisomal outer membrane that serves as the principal receptor for the cytosolic GTPase Drp1, driving organelle fission (PMID:18353969, PMID:21149567, PMID:24167709). It functions as a dynamic oligomer—most likely a trimer—whose self-association through a C-terminal coiled-coil is required to activate Drp1, with actin filaments enhancing this activation by concentrating the machinery (PMID:34347505). MFF selectively engages higher-order, assembly-competent Drp1 oligomers rather than dimers, a selectivity that distinguishes it from the MiD49/MiD51 receptors with which it co-assembles into a trimeric DRP1–MiD–MFF fission complex (PMID:26446846, PMID:34805137, PMID:39365854). Drp1 recruitment to MFF is gated by Drp1 modification state: Ser637 dephosphorylation and SENP3-mediated deSUMOylation of Drp1 both promote the MFF–Drp1 interaction and downstream cytochrome c release and apoptosis (PMID:26432782, PMID:28262828). MFF activity is itself tuned by a layered post-translational code—AMPK phosphorylation and the consequent SUMOylation at Lys151 controlling MiD levels in the fission complex during stress (PMID:39365854), PKD phosphorylation driving mitosis-specific fission needed for chromosome segregation (PMID:34010649), Parkin/PINK1 ubiquitination governing both constitutive turnover and mitophagic clearance of damaged mitochondria (PMID:26008206, PMID:31112535), and CPT1A-dependent succinylation at Lys302 protecting MFF from Parkin-mediated degradation (PMID:37291333). Physiologically, balanced MFF-driven fission is essential: its loss in mice causes lethal dilated cardiomyopathy rescued by concurrent ablation of the fusion gene Mfn1 (PMID:26598616), and in neurons FMRP-controlled local translation of MFF sets compartment-specific mitochondrial size and presynaptic calcium handling and neurotransmitter release (PMID:30479337, PMID:39548330). Beyond canonical fission, MFF nucleates active MAVS clusters on mitochondria for antiviral signaling independently of Drp1 (PMID:33177519), participates in a MARCH5/p97/Npl4 ubiquitin-ligase complex controlling MiD49 and Mcl1 stability (PMID:27932492), and mediates actin/ARP2/3-dependent melanosome fission independently of DRP1 (PMID:41832149).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2008 High

    Established MFF as a distinct, dedicated component of the mitochondrial fission machinery, separating it from the previously known Fis1/Drp1 pathway.

    Evidence RNAi in Drosophila and human cells with morphology and size-exclusion fractionation showing MFF and Fis1 in separate complexes

    PMID:18353969

    Open questions at the time
    • Did not define how MFF promotes fission molecularly
    • Relationship to Drp1 recruitment unresolved
    • Peroxisomal role noted but not mechanistically dissected
  2. 2010 High

    Identified MFF as an essential outer-membrane receptor that physically recruits Drp1 to mitochondria, defining the receptor logic of fission.

    Evidence siRNA/overexpression, in vitro and in vivo Co-IP, and CAAX membrane-retargeting redirecting Drp1 to the plasma membrane

    PMID:21149567

    Open questions at the time
    • Did not explain selectivity for Drp1 assembly states
    • Stoichiometry/oligomeric state of MFF unknown
    • Did not resolve overlap with Fis1 and MiD receptors
  3. 2013 Medium

    Resolved the redundancy among Drp1 receptors, showing MFF, Fis1, and the MiD proteins each contribute to Drp1 recruitment, and extended MFF function to peroxisomal division.

    Evidence Single and combinatorial knockout cell lines with Drp1 puncta quantification; reciprocal Co-IP and localization at peroxisomal constrictions

    PMID:23283981 PMID:24167709

    Open questions at the time
    • Quantitative hierarchy among receptors not established
    • Peroxisomal Pex11pβ–MFF Co-IP from single lab
    • Mechanism of constriction-site targeting unknown
  4. 2015 High

    Defined the molecular basis of MFF–Drp1 selectivity and demonstrated physiological necessity of MFF-driven fission in vivo.

    Evidence In vitro binding with assembly-deficient Drp1 and insert-B mutants; mouse Mff/Mfn1 double-knockout cardiac epistasis; UV-apoptosis Co-IP linking Drp1 Ser637 dephosphorylation to binding

    PMID:26432782 PMID:26446846 PMID:26598616

    Open questions at the time
    • Structural details of the higher-order-oligomer interface not solved
    • How fission/fusion imbalance kills cardiomyocytes mechanistically unclear
    • Upstream kinase/phosphatase controlling Ser637 in this context not defined
  5. 2015 Medium

    Linked MFF to the Parkin/PINK1 mitophagy axis, showing MFF ubiquitination couples fission machinery to autophagic clearance.

    Evidence CCCP depolarization, K251R mutagenesis, p62 translocation assays, and Mff knockout rescue

    PMID:26008206

    Open questions at the time
    • Single-lab Co-IP/mutagenesis
    • Whether ubiquitination acts via turnover or adaptor recruitment not fully separated
    • Other contributing ligases not identified at this stage
  6. 2016 Medium

    Placed MFF within a regulatory network with MiD51 and the MARCH5 ubiquitin-ligase complex, showing MFF both is regulated by and regulates fission-complex protein stability.

    Evidence CRISPR knockouts, BioID proximity labeling, Drp1 GTPase assays, protein half-life/ubiquitination measurements, and MARCH5/p97/Npl4 Co-IP

    PMID:27076521 PMID:27932492

    Open questions at the time
    • MARCH5 complex stoichiometry and direct contacts undefined
    • How MFF restrains MARCH5 activity mechanistically unclear
    • Single-lab epistasis for stability control
  7. 2017 Medium

    Showed that Drp1 SUMO state, controlled by SENP3, gates the MFF–Drp1 interaction and stress-induced apoptosis.

    Evidence SENP3 manipulation, Drp1 SUMO-site mutants, Co-IP, cytochrome c release, and MOM-tethering bypass

    PMID:28262828

    Open questions at the time
    • Single-lab Co-IP evidence
    • Direct contribution of SUMO to binding interface not structurally resolved
    • Physiological trigger of SENP3 activation here not defined
  8. 2018 Medium

    Expanded MFF regulation and function to phospho-control of pathological fission, neuronal mitochondrial sizing, and a Drp1-independent VDAC1 interaction exploitable in cancer.

    Evidence CK2α/NR4A1 cardiac IR model; neuronal MFF knockdown with Ca2+ imaging and release electrophysiology; VDAC1 Co-IP with peptidomimetic disruption

    PMID:29744594 PMID:30479337 PMID:31582380

    Open questions at the time
    • VDAC1 interaction and its physiological role only partly mapped
    • Neuronal phenotype mechanism downstream of size not fully traced
    • CK2α phospho-site on MFF not pinned to structure
  9. 2019 Medium

    Established that Parkin ubiquitinates MFF under basal conditions for constitutive turnover, while implicating Bcl-xL as a direct MFF partner restraining fission.

    Evidence Parkin/PINK1 shRNA with basal ubiquitination/turnover assays; FRET two-hybrid showing Bcl-xL–MFF oligomer stoichiometry and network remodeling

    PMID:31112535 PMID:31587505

    Open questions at the time
    • Additional basal MFF ligase(s) not identified
    • Bcl-xL–MFF interface and its in vivo relevance undefined
    • Single-lab FRET stoichiometry
  10. 2020 High

    Uncovered a fission-independent role for MFF as a platform that nucleates antiviral MAVS clusters, gated by AMPK phosphorylation, plus translational and apoptotic regulators of MFF.

    Evidence MAVS clustering assays with Drp1-independence tests and AMPK manipulation; Pum2 translational repression in ischemic AKI; Mcl-1 FRET showing functional inhibition without direct binding

    PMID:31941601 PMID:31993882 PMID:33177519

    Open questions at the time
    • How AMPK phosphorylation reorganizes MAVS clusters structurally unknown
    • Mcl-1 acts on MFF function indirectly by an undefined route
    • Pum2–MFF mRNA regulation mechanism not detailed
  11. 2021 High

    Defined MFF's dynamic oligomeric mechanism and its actin synergy, and added PKD-driven mitotic phosphorylation and Bcl-xL/SENP3 apoptotic coupling.

    Evidence In vitro reconstitution with TIRF and GTPase assays and oligomerization-defective rescue; in vitro PKD kinase assays with mitotic phenotyping; Co-IP/in vitro binding for MFF–Bcl-xL priming of Drp1; crosslinking analysis of Drp1 assembly-state binding by MFF versus MIEFs

    PMID:34010649 PMID:34347505 PMID:34722538 PMID:34805137

    Open questions at the time
    • Atomic structure of the trimeric scaffold lacking
    • How actin physically lowers effective MFF concentration unresolved
    • PKD phospho-site structural consequence not defined
  12. 2022 Medium

    Linked MFF to ER–mitochondrial Ca2+ handling in dopaminergic neurons and to peroxisomal MAVS control hijacked by viral immune evasion.

    Evidence MFF siRNA in dopaminergic neurons with Ca2+/ROS imaging and VDAC1 Co-IP; HCMV vMIA with MFF-dependent peroxisomal MAVS oligomerization assays

    PMID:35445031 PMID:35883852

    Open questions at the time
    • Whether VDAC1 binding directly mediates Ca2+ regulation not proven
    • Organelle specificity of vMIA–MFF dependence mechanism unclear
    • Single-lab studies
  13. 2023 Medium

    Identified succinylation at Lys302 as a PTM that stabilizes MFF against Parkin degradation, promoting fission and tumor growth.

    Evidence CPT1A manipulation, MS site mapping, K302 mutagenesis, and MFF stability/tumor assays

    PMID:37291333

    Open questions at the time
    • Single-lab PTM mapping
    • Interplay between K302 succinylation and K251 ubiquitination not resolved
    • Generality beyond ovarian cancer unknown
  14. 2024 High

    Connected the AMPK→MFF SUMOylation (K151) axis to MiD content in fission complexes, defined FMRP-driven local MFF translation at fission sites, and revealed tissue-specific splicing tuning AMPK responsiveness.

    Evidence K151R mutagenesis with KO rescue and MiD Co-IP; cryo-ET and real-time translation imaging with FMRP loss-of-function; splice-isoform rescue in Mff-KO MEFs

    PMID:39293584 PMID:39365854 PMID:39548330

    Open questions at the time
    • How SUMOylation mechanically alters MiD recruitment unresolved
    • FMRP–MFF mRNA targeting determinants not fully mapped
    • Functional impact of splice isoforms in vivo limited
  15. 2025 Medium

    Added TRIM21 as an additional E3 ligase degrading MFF, linking drug-induced MFF loss to mitochondrial dysfunction and senescence, and extended MFF function to DRP1-independent melanosome fission.

    Evidence TRIM21–MFF Co-IP, ubiquitination assays, and rescue; MFF/DRP1 comparative knockdown with ARP2/3 Co-IP and actin imaging at melanosome constrictions

    PMID:41650744 PMID:41832149

    Open questions at the time
    • TRIM21 ubiquitination site on MFF not mapped
    • How MFF couples to ARP2/3-driven actin at melanosomes mechanistically unclear
    • Single-study findings

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the dynamic MFF oligomer engaging higher-order Drp1 (and its integration with MiD proteins) remains undefined, leaving the physical basis of receptor selectivity, actin synergy, and PTM control unresolved.
  • No atomic structure of the MFF trimer or MFF–Drp1 interface
  • Unified model integrating ubiquitination/SUMOylation/succinylation/phosphorylation on a single MFF molecule lacking
  • Direct vs indirect basis of several fission-independent roles unresolved

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 3 GO:0005777 peroxisome 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
BCL2L1DNM1LFMR1MARCH5MIEF1MIEF2PEX11BVDAC1
Complex memberships
DRP1–MiD–MFF fission complexMARCH5/p97/Npl4 ubiquitin-ligase complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MFF is a tail-anchored protein of the mitochondrial outer membrane that controls mitochondrial fission; siRNA knockdown causes a closed mitochondrial network phenotype similar to Drp1/Fis1 knockdown, and MFF and Fis1 exist in separate ~200 kDa complexes, suggesting distinct roles in fission. MFF knockdown also inhibits peroxisomal fission. siRNA screen in Drosophila cells, human cell siRNA knockdown, co-immunoprecipitation/size-exclusion to distinguish MFF and Fis1 complexes, mitochondrial/peroxisomal morphology assays Molecular biology of the cell High 18353969
2010 MFF is an essential mitochondrial outer membrane receptor for Drp1 recruitment: MFF knockdown releases Drp1 foci from the MOM with network extension; overexpression stimulates Drp1 recruitment and fission; MFF and Drp1 physically interact in vitro and in vivo; MFF-dependent fission is independent of Fis1; retargeting MFF to the plasma membrane via a CAAX motif redirects Drp1 to that membrane; MFF knockdown compromises stimulus-induced fission and apoptosis. siRNA knockdown, overexpression, in vitro and in vivo co-immunoprecipitation/pulldown, CAAX membrane-retargeting assay, apoptosis assay The Journal of cell biology High 21149567
2013 Both MFF and Fis1 contribute to Drp1 recruitment and mitochondrial fission; MFF-null and Fis1-null cells each show reduced Drp1 puncta size/number on mitochondria; MiD49 and MiD51 can independently mediate Drp1 recruitment and fission in the absence of both Fis1 and Mff. Gene knockout cell lines (Fis1-null, Mff-null, Fis1/Mff-null), immunofluorescence of Drp1 puncta, mitochondrial morphology analysis Molecular biology of the cell High 23283981
2013 MFF functions with Pex11pβ and DLP1 (Drp1) in peroxisomal fission: endogenous MFF localizes to peroxisomal membrane-constricted regions; MFF knockdown abolishes the fission stage of peroxisomal division and prevents DLP1 recruitment to peroxisomes; MFF overexpression increases DLP1 peroxisomal targeting and increases Pex11pβ–DLP1 interaction; Pex11pβ interacts with Mff in a DLP1-dependent manner. siRNA knockdown, overexpression, co-immunoprecipitation, immunofluorescence localization Biology open Medium 24167709
2015 MFF selectively binds oligomerized (higher-order) Drp1 but not assembly-deficient Drp1 mutants; the insert B region of Drp1 inhibits Mff–Drp1 interaction; recombinant Drp1 lacking insert B forms a stable complex with Mff; in contrast, MiD51/MiD49 can recruit Drp1 dimers, explaining divergent outcomes of overexpression. Genetic and biochemical assays with recombinant proteins, pulldown with assembly-deficient Drp1 mutants, in vitro binding Molecular biology of the cell High 26446846
2015 Mff-deficient mice develop lethal dilated cardiomyopathy with reduced mitochondrial density and respiratory chain activity and increased mitophagy; concurrent deletion of the fusion gene Mfn1 completely rescues heart dysfunction, lifespan, and respiratory chain function, demonstrating that rebalancing fission/fusion restores organ physiology. Mouse knockout and double-knockout genetics, cardiac function assessment, electron microscopy, respiratory chain activity assay, mitophagy markers The Journal of cell biology High 26598616
2015 The phosphorylation status of Drp1 at Ser637 is essential for its interaction with Mff; UV irradiation reduces cytoplasmic and mitochondrial Drp1 Ser637 phosphorylation and enhances the Drp1–Mff interaction, leading to mitochondrial fragmentation; Mff-mediated Drp1 recruitment does not require Bax. UV irradiation apoptosis model, co-immunoprecipitation of Drp1 and Mff, phospho-Drp1 western blot, Bax-null cell experiments FASEB journal Medium 26432782
2015 Parkin ubiquitinates Mff at lysine 251 upon mitochondrial depolarization; K251R mutation abolishes Parkin-stimulated ubiquitination; ubiquitinated Mff promotes association with the autophagic adapter p62/SQSTM1; Mff knockout impairs p62 translocation to damaged mitochondria and Parkin translocation, blocking mitophagy clearance. CCCP-induced mitochondrial depolarization, co-immunoprecipitation, site-directed mutagenesis (K251R), Mff knockout rescue experiments, immunofluorescence Acta biochimica et biophysica Sinica Medium 26008206
2016 MiD51 suppresses Mff-dependent enhancement of Drp1 GTPase activity; proximity-based biotin labeling (BioID) shows close associations between MiD51, Mff, and Drp1 but not Fis1; combined loss of MiD51 and Mff further enhances mitochondrial connectivity compared to single knockouts. CRISPR/Cas9 gene editing, BioID proximity labeling, Drp1 GTPase activity assay, mitochondrial morphology analysis Journal of cell science High 27076521
2016 Mff and Drp1 negatively regulate MARCH5 E3 ubiquitin ligase activity toward MiD49 and Mcl1; Mff knockout leads to reduced expression, shorter half-lives, and increased ubiquitination of MiD49 and Mcl1 via MARCH5; Mff is an integral component of the MARCH5/p97/Npl4 complex. Mff and Drp1 knockout cells, MARCH5 knockout double-mutant cells, protein half-life assays, ubiquitination assays, co-immunoprecipitation of MARCH5/p97/Npl4/Mff complex Molecular biology of the cell Medium 27932492
2017 SENP3-mediated deSUMOylation of Drp1 promotes Drp1 binding to Mff on the mitochondrial outer membrane; preventing Drp1 SUMOylation (SUMO-site mutant) enhances Mff binding; knocking down SENP3 reduces Drp1–Mff interaction and stress-induced cytochrome c release; directly tethering Drp1 to the MOM bypasses the need for Mff and occludes the SENP3 effect. SENP3 overexpression/knockdown, SUMO-site Drp1 mutants, co-immunoprecipitation, cytochrome c release assay, Drp1 MOM-tethering construct Scientific reports Medium 28262828
2018 CK2α phosphorylates MFF downstream of NR4A1 activation during cardiac microvascular IR injury; phosphorylated MFF enhances cytoplasmic Drp1 translocation to mitochondria, causing fatal mitochondrial fission. NR4A1 knockout mice, in vitro endothelial cell model, CK2α inhibitor, western blot for phospho-Mff, immunofluorescence for Drp1 translocation Basic research in cardiology Medium 29744594
2018 MFF overexpression forms homo- and heterodimeric complexes with VDAC1 via key contact residues (Arg225, Arg236, Gln241); a cell-permeable MFF peptidomimetic disrupts the MFF-VDAC1 complex, acutely depolarizes mitochondria, and triggers cell death in tumor but not normal cells. Co-immunoprecipitation, mutational analysis of contact residues, peptidomimetic functional assay, mitochondrial membrane potential assay, in vitro cell death assays Cancer research Medium 31582380
2018 MFF is required for axonal mitochondrial size maintenance: MFF downregulation in cortical pyramidal neurons increases presynaptic mitochondrial size, augments mitochondrial Ca2+ uptake during neurotransmission, reduces presynaptic Ca2+ accumulation, decreases neurotransmitter release, and reduces terminal axon branching; MFF does not affect mitochondrial trafficking, presynaptic capture, membrane potential, or ATP generation. In vitro and in vivo MFF knockdown in cortical neurons, live imaging of mitochondria and Ca2+, electrophysiology/release assays, axon branching quantification Nature communications High 30479337
2019 Parkin ubiquitinates Mff in a PINK1-dependent manner under non-stressed (basal) conditions to regulate constitutive Mff turnover; shRNA-mediated Parkin knockdown does not completely prevent basal Mff ubiquitination, indicating at least one additional ubiquitin ligase contributes to Mff proteostasis. Parkin/PINK1 shRNA knockdown, ubiquitination assays under non-stressed conditions, protein turnover assay PloS one Medium 31112535
2020 MAVS is activated by Mff through formation of active MAVS clusters on mitochondria, independent of mitochondrial fission and Drp1; under mitochondrial dysfunction, AMPK phosphorylates Mff, leading to disorganization of MAVS clusters and repression of the acute antiviral response; Mff also contributes to immune tolerance during chronic infection by disrupting mitochondrial MAVS clusters. Cell culture overexpression/knockdown, AMPK activation/inhibition, MAVS clustering assays, antiviral signaling readouts, Drp1-independent assays Nature communications High 33177519
2020 Pum2 (RNA-binding protein) negatively regulates Mff mRNA translation; in ischemic AKI, Pum2 is downregulated, inversely correlating with Mff upregulation; Pum2 overexpression reduces Mff protein levels and protects against mitochondrial fission-dependent renal injury. Mff genetic deletion mouse model, Pum2 overexpression, western blot for Pum2/Mff correlation, ischemic AKI mouse model Cell biology and toxicology Medium 31993882
2021 Mff is an oligomer (most likely trimer) that dynamically associates/disassociates 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 the effective Mff concentration ~10-fold; Mff interacts with Drp1 on actin filaments in an oligomerization-dependent manner; oligomerization-defective Mff fails to rescue mitochondrial/peroxisome division, Drp1 recruitment, or Mff puncta formation in Mff-KO cells. In vitro reconstitution with purified proteins, TIRF microscopy, Drp1 GTPase activation assay, Mff-KO rescue with oligomerization-defective mutants, U2OS cell division/morphology assays Molecular biology of the cell High 34347505
2021 PKD (Protein Kinase D) directly phosphorylates MFF specifically during mitosis; PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not interphase cells; MFF phosphorylation is crucial for chromosome segregation and cell survival by inhibiting adaptation of the mitotic checkpoint. In vitro kinase assay, phospho-MFF site identification, PKD inhibition/overexpression, mitosis-specific cell imaging, chromosome segregation assay Cell reports High 34010649
2021 Mff primes Drp1 binding to Bcl-xL at mitochondria; Mff and Bcl-xL can interact directly, independent of Drp1, through their transmembrane domains; SENP3-mediated deSUMOylation of Drp1 promotes the Drp1–Bcl-xL interaction; recovery of SENP3 after OGD/reoxygenation promotes the Drp1–Bcl-xL interaction and cell death. Co-immunoprecipitation, in vitro binding assays, SUMO-site Drp1 mutants, OGD model, Bcl-xL mutant with defective Drp1 binding Frontiers in cell and developmental biology Medium 34722538
2021 Mff preferentially binds higher-order oligomers of Drp1, while MIEFs bind a wider range of Drp1 assembly states including lower oligomers; forced Drp1 recruitment by either Mff or MIEFs facilitates Drp1 oligomerization on mitochondria; MIEFs serve as a platform facilitating Drp1 binding to Mff, and loss of MIEFs severely impairs Drp1–Mff interaction. In vivo chemical crosslinking, co-immunoprecipitation with oligomerization and GTPase-deficient Drp1 mutants, Mff/MIEF1/2-deficient cell lines Frontiers in cell and developmental biology Medium 34805137
2022 Human HCMV vMIA inhibits MAVS oligomerization at peroxisomes in an MFF-dependent manner; vMIA is totally dependent on MFF (the organelle fission machinery) to induce peroxisomal fragmentation, while this dependency is not observed at mitochondria; vMIA interacts with MAVS at peroxisomes and inhibits its oligomerization. HCMV infection, vMIA expression, MFF knockdown/knockout, MAVS oligomerization assay, peroxisomal and mitochondrial morphology analysis Frontiers in cell and developmental biology Medium 35445031
2023 CPT1A promotes succinylation of MFF at lysine 302 (K302) through its lysine succinyltransferase (LSTase) activity; K302 succinylation protects MFF against Parkin-mediated ubiquitin-proteasomal degradation; elevated MFF succinylation promotes mitochondrial fission and ovarian cancer cell growth. CPT1A overexpression/knockdown, mass spectrometry identification of K302 succinylation site, site-directed mutagenesis, MFF protein stability assay with Parkin, in vivo tumor model Communications biology Medium 37291333
2024 MFF is SUMOylated at Lys151; MFF SUMOylation is enhanced following AMPK-mediated phosphorylation; MFF SUMOylation regulates the level of MiD (MiD49/51) binding to MFF in the trimeric DRP1-MiD-MFF complex; CCCP-induced mitochondrial fragmentation is impaired in MFF-KO MEFs expressing non-SUMOylatable MFF K151R, demonstrating that AMPK→MFF SUMOylation dynamically controls stress-induced fragmentation by modulating MiD levels in fission complexes. Site-directed mutagenesis (K151R), SUMO assay, AMPK activation, MFF-KO MEF rescue, CCCP treatment, co-immunoprecipitation for MiD–MFF interaction Science advances High 39365854
2024 FMRP granules are recruited to the mitochondrial midzone (fission sites) in axons and dendrites; FMRP promotes local translation of MFF at mitochondria-associated ribosome-rich granules, specifically enabling replicative fission at the mitochondrial midzone; disrupting FMRP function dysregulates MFF translation and causes increased peripheral fission and irregular mitochondrial nucleoid distribution. Cryo-electron tomography, real-time translation imaging, FMRP granule live imaging, FMRP loss-of-function, mitochondrial fission site imaging, nucleoid distribution assay Nature cell biology High 39548330
2024 Mouse Mff has tissue-specific alternative splicing; insertion of exon 6 just after the AMPK phosphorylation site reduces AMPK-mediated Mff phosphorylation and impairs both mitochondrial fission and MAVS-dependent antiviral response functions; this splicing effect is independent of phosphorylation per se. Splice isoform introduction into Mff-KO MEFs, AMPK phosphorylation assay, mitochondrial fission assay, antiviral signaling assay Pharmacological research Medium 39293584
2026 MFF is trafficked between mitochondria and melanosomes and localizes at melanosome fission events; MFF downregulation (but not DRP1 knockdown) causes melanosome enlargement, intracellular melanin accumulation, and increased lumenal catabolism; MFF interacts with regulators of the ARP2/3 complex; actin filaments accumulate between melanosomes at MFF-enriched constriction sites; ARP2/3 subunit silencing mimics MFF loss, indicating MFF mediates actin-dependent melanosome fission independently of DRP1. MFF downregulation, DRP1 knockdown comparison, live imaging of MFF trafficking, immunofluorescence at fission sites, ARP2/3 co-immunoprecipitation, ARP2/3 knockdown phenocopy Nature communications Medium 41832149
2022 MFF-insufficiency (siRNA) in dopaminergic neurons causes impaired neurite outgrowth, mitochondrial Ca2+ accumulation via accelerated Ca2+ influx from the ER through the InsP3R, excessive mitochondrial ROS production, and downregulation of PGC-1α; MFF co-immunoprecipitates with VDAC1, an essential component of the ER-mitochondrial Ca2+ transport system, suggesting MFF negatively regulates mitochondrial Ca2+ influx from the ER. MFF siRNA in stem cell-derived dopaminergic neurons, Ca2+ imaging, ROS measurement, co-immunoprecipitation of MFF and VDAC1, neurite outgrowth assay Antioxidants Medium 35883852
2019 Bcl-xL interacts with Mff to form heterogeneous oligomers with 1:2 stoichiometry in cytoplasm and 1:1 stoichiometry on mitochondria; Bcl-xL coexpression reconstructs the Mff network from punctate higher-order oligomers to filamentous lower-order oligomers; Bcl-xL inhibits Mff-mediated mitochondrial fragmentation and apoptosis. Live-cell FRET two-hybrid assay, fluorescence microscopy, oligomer distribution analysis FEBS open bio Medium 31587505
2020 Mcl-1 inhibits Mff-mediated mitochondrial fragmentation and apoptosis; however, Mcl-1 does NOT directly bind to Mff on mitochondria (negative finding confirmed by FRET analysis in live cells). Live-cell co-expression, FRET efficiency measurement, mitochondrial morphology and apoptosis assays Biochemical and biophysical research communications Medium 31941601
2025 TRIM21 E3 ubiquitin ligase mediates ubiquitination and proteasomal degradation of MFF; ciprofloxacin exposure upregulates TRIM21, promotes TRIM21-mediated MFF degradation, and the resulting reduction in MFF causes mitochondrial dysfunction and cell senescence in trophoblasts. Co-immunoprecipitation of TRIM21-MFF, ubiquitination assay, TRIM21 overexpression/knockdown, MFF rescue experiments EBioMedicine Medium 41650744

Source papers

Stage 0 corpus · 80 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 1008 23283981
2010 Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. The Journal of cell biology 907 21149567
2008 The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Molecular biology of the cell 621 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 405 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 278 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 277 29744594
2016 Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. Journal of cell science 265 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 248 23921378
2018 MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. Nature communications 215 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 139 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 100 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 79 27932492
2018 DUSP1 recuses diabetic nephropathy via repressing JNK-Mff-mitochondrial fission pathways. Journal of cellular physiology 71 30191967
2020 Pum2-Mff axis fine-tunes mitochondrial quality control in acute ischemic kidney injury. Cell biology and toxicology 70 31993882
2017 SENP3-mediated deSUMOylation of Drp1 facilitates interaction with Mff to promote cell death. Scientific reports 65 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 52 33177519
2020 Drp1/Mff signaling pathway is involved in fluoride-induced abnormal fission of hepatocyte mitochondria in mice. The Science of the total environment 51 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 44 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 38 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 29 39548330
2022 AMPK/MFF Activation: Role in Mitochondrial Fission and Mitophagy in Dry Eye. Investigative ophthalmology & visual science 29 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 27 33763168
2021 A PKD-MFF signaling axis couples mitochondrial fission to mitotic progression. Cell reports 27 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 25 29496454
2023 Kaempferol induces mitochondrial dysfunction and mitophagy by activating the LKB1/AMPK/MFF pathway in breast precancerous lesions. Phytotherapy research : PTR 23 37086359
2025 CPT1A-mediated MFF succinylation promotes stemness maintenance in ovarian cancer stem cells. Communications biology 21 39956875
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
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 17 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 15 38682264
2024 SUMOylation of MFF coordinates fission complexes to promote stress-induced mitochondrial fragmentation. Science advances 15 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 11 34722538
2024 Alternative splicing of Mff regulates AMPK-mediated phosphorylation, mitochondrial fission and antiviral response. Pharmacological research 10 39293584
2023 Senomorphic effect of diphenyleneiodonium through AMPK/MFF/DRP1 mediated mitochondrial fission. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 9 37004322
2022 iTTCA-MFF: identifying tumor T cell antigens based on multiple feature fusion. Immunogenetics 7 35246701
2022 Mitochondrial fission factor (MFF) frameshift variant in Bullmastiffs with mitochondrial fission encephalopathy. Animal genetics 7 36085405
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
2024 MFF-DTA: Multi-scale feature fusion for drug-target affinity prediction. Methods (San Diego, Calif.) 4 39218169
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 MFF-nDA: A Computational Model for ncRNA-Disease Association Prediction Based on Multimodule Fusion. Journal of chemical information and modeling 3 40129032
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
2023 A Heterozygous Mutation in MFF Associated with a Mild Mitochondrial Phenotype. Journal of neuromuscular diseases 3 36314214
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
2026 Targeting MFF succinylation: a novel therapeutic strategy for premature ovarian insufficiency by restoring mitochondrial dynamics in granulosa cells. Journal of ovarian research 1 41549306
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
2025 MicroRNA-27b alleviates septic cardiomyopathy by targeting the Mff/MAVS axis. Frontiers in cellular and infection microbiology 1 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 1 41116985
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
2026 MFF Promotes Aggressive Phenotypes and Immunosuppression in Lung Adenocarcinoma via Mitochondrial Dysregulation. Current medicinal chemistry 0 42220150
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 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

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