Affinage

MFN2

Mitofusin-2 · UniProt O95140

Length
757 aa
Mass
86.4 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 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

MFN2 is a dynamin-like GTPase that drives mitochondrial fusion and serves as a master organizer of inter-organelle contact sites, coordinating mitochondrial dynamics, calcium homeostasis, quality control, and metabolic signaling (PMID:12527753, PMID:34296790). Together with its paralog MFN1, it is required for mammalian mitochondrial fusion, forming functional homotypic and heterotypic complexes whose loss causes fragmentation and membrane-potential collapse (PMID:12527753); fusion proceeds through GTP-dependent cis-oligomerization gated by an intramolecular interaction (Met376/His380–Asp725/Leu727) that is controlled by PINK1 phosphorylation of adjacent Ser378, and that can be pharmacologically activated to rescue CMT2A-mutant defects (PMID:29674596, PMID:32245838). A distinct ER-localized pool of MFN2 tethers ER to mitochondria by trans-interaction with mitochondrial MFN1/2, enabling ER-to-mitochondria Ca2+ transfer that supports bioenergetics and neuritic outgrowth, acting through contact-site machinery including IP3R3-Grp75 and VAPB-PTPIP51 and engaging SERCA2 to balance Ca2+ flux (PMID:34296790, PMID:34110411, PMID:37738362). Beyond classical MAMs, MFN2 nucleates contacts with lipid droplets via Hsc70 for fatty-acid transfer, with melanosomes, peroxisomes, and the nuclear envelope, where it tethers mitochondria to enable non-canonical nuclear import of the pyruvate dehydrogenase complex (PMID:38311582, PMID:24485836, PMID:35523862, PMID:35245450). MFN2 also functions as a signaling brake, repressing PERK kinase activity at the ER, suppressing Ras-Raf-ERK and mTORC2/Akt pathways through domain-specific interactions, and recruiting ATAT1 to mitochondria-microtubule contacts to regulate α-tubulin acetylation and mitochondrial transport (PMID:23921556, PMID:24081906, PMID:28176801, PMID:38883841). MFN2 abundance and fusion activity are tightly set by post-translational control: PGAM5 dephosphorylation protects it from degradation, while phosphorylation by PINK1 and LRRK2 and ubiquitination by Parkin, MITOL, RBCK1, and Mul1 (reversed by USP2) couple MFN2 to mitophagy and stress responses (PMID:37498743, PMID:37633049, PMID:30219582, PMID:34870686, PMID:38763208, PMID:37100191). Mutations in MFN2 cause Charcot-Marie-Tooth type 2A, and a D210V mutation produces multiple mtDNA deletions, establishing that fusion-competent MFN2 is required for mtDNA stability (PMID:29674596, PMID:22189565).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 High

    Established that MFN2, with MFN1, is essential for mammalian mitochondrial fusion and that fusion is protective, defining the gene's core cell-biological function.

    Evidence Mfn1/Mfn2 knockout MEFs with morphology imaging, genetic rescue, and reciprocal Co-IP

    PMID:12527753

    Open questions at the time
    • Did not resolve the molecular fusion mechanism or GTPase cycle
    • Did not address non-fusion functions
  2. 2011 Medium

    Linked MFN2 dysfunction to genomic instability of the mitochondrial genome, showing fusion is required to maintain mtDNA integrity.

    Evidence Clinical genetics of MFN2 D210V with patient muscle mtDNA deletion analysis and fibroblast repair assays

    PMID:22189565

    Open questions at the time
    • Single family study
    • Mechanism connecting fusion loss to deletion accumulation not defined
  3. 2013 High

    Identified MFN2 as a signaling regulator, not just a structural fusion protein, by showing it represses PERK at the ER and thereby controls ROS and mitochondrial Ca2+.

    Evidence Reciprocal Co-IP and siRNA epistasis in MEFs under ER stress with ROS/Ca2+/morphology readouts; later corroborated in podocytes

    PMID:23921556 PMID:34988075

    Open questions at the time
    • Whether repression is direct enzymatic inhibition or contact-dependent unclear
    • Structural basis of MFN2-PERK interaction unknown
  4. 2013 Medium

    Mapped MFN2 anti-proliferative signaling to distinct domains acting on the Ras-Raf-ERK axis.

    Evidence Domain-fragment Co-IP and rescue in KO MEFs and BJAB cells with proliferation assays

    PMID:24081906

    Open questions at the time
    • Single lab
    • Direct versus scaffold role in pathway inhibition not separated
  5. 2014 Medium

    Extended MFN2-dependent contact sites beyond ER to melanosomes, implicating it in secretory organelle biogenesis.

    Evidence Electron tomography of mitochondria-melanosome contacts with knockdown and melanogenesis assays

    PMID:24485836

    Open questions at the time
    • Molecular tether at the melanosome interface unidentified
    • Single lab
  6. 2016 High

    Connected MFN2 loss to mitochondrial quality control by revealing a compensatory ROS-HIF1α-BNIP3 mitophagy axis in muscle.

    Evidence Skeletal muscle-specific Mfn2 KO mice with mitophagy, ROS, and expression profiling

    PMID:27334614

    Open questions at the time
    • Direct molecular trigger of the adaptive pathway not defined
    • Tissue-specificity of compensation unclear
  7. 2017 High

    Defined paralog-specific roles for MFN2 in metabolic tissues, tethering mitochondria to lipid droplets via perilipin 1 and suppressing mTORC2/Akt via HR1.

    Evidence Adipose-specific KO with Co-IP and respirometry; CRISPR MFN2 KO with domain-mapped mTORC2 Co-IP and xenografts

    PMID:28176801 PMID:28348166

    Open questions at the time
    • Why MFN1 cannot substitute mechanistically unresolved
    • mTORC2 finding is single lab, Medium confidence
  8. 2018 High

    Resolved the intramolecular conformational switch governing fusion and showed PINK1 phosphorylates Ser378 to control it, enabling small-molecule MFN2 agonists.

    Evidence Interface-residue mutagenesis, in vitro PINK1 kinase assays, and agonist treatment in neurons and a CMT2A mouse model

    PMID:29674596

    Open questions at the time
    • In vivo phospho-occupancy and dynamics of Ser378 not quantified
    • How agonists distinguish open versus closed states structurally incomplete
  9. 2018 High

    Showed Parkin-dependent ubiquitination of MFN2 is required for ER-mitochondria tethering, coupling a mitophagy ligase to contact-site function.

    Evidence Non-ubiquitinatable MFN2 mutant rescue, Parkin-deficient patient fibroblasts, Co-IP, and Drosophila PD rescue with synthetic linker

    PMID:30219582

    Open questions at the time
    • Specific ubiquitin chain type and topology not defined
    • How ubiquitination promotes tethering rather than degradation mechanistically unclear
  10. 2020 High

    Demonstrated in vitro that CMT2A hinge variants impair GTP-dependent cis-oligomerization and fusion, and that cytosolic factors including Bax can compensate.

    Evidence Reconstituted proteoliposome fusion and nucleotide-assembly assays with defined variants plus Bax/cytosol addition

    PMID:32245838

    Open questions at the time
    • Identity of compensating cytosolic factors beyond Bax unknown
    • Physiological relevance of Bax rescue in neurons untested
  11. 2020 High

    Placed MFN2 in energy-stress autophagy by showing AMPK directly engages it to drive MAM formation, a paralog-specific role.

    Evidence AMPK-MFN2 Co-IP, Mfn2-null rescue MEFs, EM quantification of MAMs, and metabolic assays

    PMID:32249716

    Open questions at the time
    • Whether AMPK phosphorylates MFN2 directly not established
    • Order of MAM formation versus autophagy induction unresolved
  12. 2021 High

    Separated MFN2's ER-localized tethering/bioenergetic function from its mitochondrial fusion function using organelle-targeted constructs.

    Evidence ER- versus mitochondria-targeted Mfn2 rescue in KO neurons with Ca2+ transfer, bioenergetics, and neurite assays; in vivo conditional KO with EM and contact-marker Co-IP

    PMID:34110411 PMID:34296790

    Open questions at the time
    • Stoichiometry of ER-Mfn2/mito-Mfn1-2 trans-complex not defined
    • How the two pools are partitioned in cells unclear
  13. 2021 Medium

    Identified VCP cofactor UBXN1 as the machinery extracting MFN2 from the OMM during PRKN-dependent mitophagy.

    Evidence UBXN1 KO cells, Co-IP, fractionation, and super-resolution imaging of MFN2 blobs with mitophagy flux

    PMID:33966597

    Open questions at the time
    • Single lab
    • Whether UBXN1 acts on all ubiquitinated MFN2 pools unclear
  14. 2021 Medium

    Established a paralog-distinct requirement for MFN2 in spermatogenesis via dual mitochondrial and ER functions and translational regulation of germ-cell mRNAs.

    Evidence Germ-cell conditional KO with organelle-targeted rescue; Co-IP with nuage proteins and MSY2 plus polysome fractionation

    PMID:32330448 PMID:33674260

    Open questions at the time
    • Mechanism linking ER/mito function to translation unresolved
    • Single lab
  15. 2022 Medium

    Broadened MFN2's contact-site repertoire to peroxisomes and the nuclear envelope, the latter enabling non-canonical nuclear import of PDC.

    Evidence BioID and dominant-negative truncations for peroxisomes; super-resolution imaging, fractionation, NPC blockade, and PDC-lamin A Co-IP for nuclear envelope

    PMID:35245450 PMID:35523862

    Open questions at the time
    • Trans-partner at peroxisome and nuclear envelope interfaces unidentified
    • Functional consequence of nuclear PDC incompletely defined
  16. 2022 Medium

    Identified MFN2 as a regulator of metabolic enzyme stability and a hub for receptor downregulation through partner-dependent ubiquitination/dephosphorylation at mitochondria.

    Evidence PFK1-TRIM21 degradation via MFN2 C-terminus (Co-IP, SPR, metabolomics, vein graft) and EGFR-Rab21-MFN2-PTPRJ axis (BLI, Co-IP, kidney KO, xenografts)

    PMID:35450439 PMID:37378422

    Open questions at the time
    • Generality of MFN2 as a degradation adaptor versus context-specific unclear
    • Each axis is single lab
  17. 2022 Medium

    Characterized how CMT2A R364W perturbs contact-site stability and shifts the MITOL/DRP1 fission-fusion balance toward hyperfusion.

    Evidence MITOL Co-IP with WT versus R364W, DRP1 ubiquitylation/degradation assays, and MAM/Ca2+ measurements

    PMID:34870686 PMID:35924634

    Open questions at the time
    • MAM-contact finding is Low confidence, overexpression-based
    • How a single residue rewires ligase availability mechanistically incomplete
  18. 2023 Medium

    Established phospho-regulation as a master switch on MFN2 stability and fate, with PGAM5 dephosphorylation favoring fusion and LRRK2 phosphorylation driving degradation.

    Evidence PGAM5-MFN2 Co-IP with phospho/ubiquitin assays and Drosophila epistasis; LRRK2-MKK4/JNK phospho-Ser27 mapping with KO mice

    PMID:37498743 PMID:37633049

    Open questions at the time
    • Which phosphosites PGAM5 targets not fully mapped
    • Integration of competing kinase/phosphatase inputs unresolved
  19. 2023 Medium

    Connected MFN2-controlled mitochondrial integrity to innate immune and Ca2+ signaling, including cGAS-STING activation upon mtDNA release and SERCA2-tuned Ca2+ in CD8+ T cells.

    Evidence Microglial Sting KO and Mfn2 knockdown with cytosolic mtDNA and pathway assays; CD8+ T cell Mfn2 ablation with SERCA2 Co-IP and tumor models

    PMID:37738362 PMID:38009491

    Open questions at the time
    • Direct cause of mtDNA leakage from fusion imbalance not pinpointed
    • Each context single lab
  20. 2024 Medium

    Revealed MFN2 control of the microtubule cytoskeleton and refined its endogenous interactome, linking transport and nutrient-responsive partners.

    Evidence MFN2-ATAT1 Co-IP with KO and CMT2A mutant live imaging; CRISPR HA-tagged endogenous interactome by MS validating RAB5C and SLC27A2

    PMID:38883841 PMID:39675054

    Open questions at the time
    • How CMT2A mutants fail to release ATAT1 structurally unknown
    • Functional roles of newly validated interactors only partly defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many post-translational inputs (PINK1, LRRK2, PGAM5, Parkin/MITOL/RBCK1/Mul1, USP2) and the ER-versus-mitochondrial pools are integrated in real time to set MFN2's choice among fusion, tethering, and degradation remains unresolved.
  • No unified quantitative model of competing PTMs on MFN2
  • Structures of trans-tethering and contact-site complexes lacking
  • Mechanism partitioning ER versus mitochondrial MFN2 pools unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0003924 GTPase activity 2 GO:0005198 structural molecule activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005739 mitochondrion 2 GO:0005811 lipid droplet 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ATAT1HSC70IP3R3MFN1PERKPFK1RAB21SERCA2
Complex memberships
ER-mitochondria tether (MAM)MFN1-MFN2 fusion complexmitochondria-lipid droplet contact (Hsc70)

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Mfn1 and Mfn2 are both required for mitochondrial fusion in mammalian cells; loss of either causes severe mitochondrial fragmentation. Mfn1 and Mfn2 form homotypic (Mfn1-Mfn1, Mfn2-Mfn2) and heterotypic (Mfn1-Mfn2) complexes, and homotypic complexes are functional for fusion. A subset of mitochondria in mutant cells lose membrane potential, indicating that fusion has a protective role. Mfn1 and Mfn2 knockout mouse embryonic fibroblasts, mitochondrial morphology imaging, genetic rescue, co-immunoprecipitation to detect homotypic and heterotypic complexes The Journal of cell biology High 12527753
2013 Mfn2 physically interacts with PERK at the ER and acts as an upstream repressor of PERK kinase activity. Mfn2-ablated cells show sustained basal PERK activation; PERK silencing in Mfn2-null cells reduces ROS production, normalizes mitochondrial calcium, and improves mitochondrial morphology. Co-immunoprecipitation to detect Mfn2-PERK interaction; siRNA knockdown of Mfn2, PERK, and XBP-1 in MEFs with ER stress induction; measurement of ROS, mitochondrial calcium, and morphology The EMBO journal High 23921556
2016 Mfn2 deficiency in skeletal muscle reduces autophagy and impairs mitochondrial quality. Aging-induced Mfn2 decrease triggers a ROS-dependent adaptive signaling pathway via HIF1α and BNIP3 to compensate for lost mitophagy and minimize mitochondrial damage. Skeletal muscle-specific Mfn2 knockout mice; gene expression profiling, mitophagy/autophagy assays, ROS and HIF1α/BNIP3 measurements The EMBO journal High 27334614
2018 MFN2 fusion activity is regulated by an intramolecular interaction between Met376/His380 and Asp725/Leu727; PINK1 kinase phosphorylates adjacent Ser378, controlling this interaction. Small-molecule mimics of this peptide-peptide interface allosterically activate MFN2 and promote mitochondrial fusion, overcoming dominant CMT2A-mutant MFN2-induced mitochondrial defects. Mutagenesis of MFN2 interaction residues; PINK1 kinase phosphorylation assays; small-molecule agonist treatment in cultured neurons and CMT2A mouse model; assessment of mitochondrial trafficking, morphology, membrane potential Science (New York, N.Y.) High 29674596
2017 Mfn2 directly interacts with perilipin 1 in brown adipose tissue, facilitating physical and functional contacts between mitochondria and lipid droplets in response to adrenergic stimulation. Mfn2, but not Mfn1, deficiency in BAT leads to impaired respiratory capacity and blunted adrenergic response. Adipose-specific Mfn2 knockout mice; Co-immunoprecipitation of Mfn2-perilipin 1; confocal imaging of mitochondria-lipid droplet contacts; respiratory capacity measurements The EMBO journal High 28348166
2020 AMPK directly interacts with MFN2 and translocates to the MAM and mitochondria under energy stress. MFN2 (but not MFN1) is required for energy stress-induced autophagy and MAM formation; re-expression of MFN2 in Mfn2-null MEFs rescues autophagy defects. Co-immunoprecipitation of AMPK-MFN2; Mfn2-knockout and Mfn2-null rescue MEFs; MAM quantification by electron microscopy; oxygen consumption rate and glycolysis measurements Autophagy High 32249716
2023 MFN2 physically interacts with SERCA2 (ER-embedded Ca2+-ATPase) at mitochondria-ER contact sites in CD8+ T cells, enhancing ER-mitochondria tethering and facilitating mitochondrial Ca2+ influx for efficient mitochondrial metabolism. MFN2 also stimulates SERCA2 ER Ca2+ retrieval activity, preventing excessive mitochondrial Ca2+ accumulation and apoptosis. Genetic ablation of Mfn2 in CD8+ T cells; Co-immunoprecipitation of MFN2-SERCA2; Ca2+ flux measurements; mitochondrial metabolic assays; tumor immunotherapy models Science immunology High 37738362
2022 MFN2 drives mitochondria to cluster and tether onto the nuclear envelope via MFN2-enriched contact points. Mitochondrial PDC (pyruvate dehydrogenase complex) crosses the nuclear envelope through a non-canonical pathway (independent of nuclear pore complexes) at these MFN2-dependent tethering sites, interacting with lamin A; reduced nuclear MFN2 decreases mitochondria tethering and nuclear PDC levels. Live imaging and super-resolution microscopy of mitochondria-nuclear envelope contacts; nuclear fractionation; pharmacological NPC blockade; Co-immunoprecipitation of PDC-lamin A; siRNA knockdown of MFN2 Molecular cell High 35245450
2021 Mfn2 localization to the ER (not mitochondria) is required for its bioenergetic function. ER-located Mfn2 interacts with mitochondrial Mfn1/2 to tether ER and mitochondria, enabling Ca2+ transfer from ER to mitochondria, which enhances mitochondrial metabolism. This ER-localized function is also necessary for proper neuritic outgrowth. ER-targeted vs. mitochondria-targeted Mfn2 constructs in Mfn2 KO neurons; Co-immunoprecipitation; Ca2+ transfer assays; mitochondrial bioenergetics measurements; neurite outgrowth assays; artificial ER-mitochondria tether rescue EMBO reports High 34296790
2021 In vivo Mfn2 conditional knockout in hippocampal and cortical pyramidal neurons reduces ER-mitochondria close contacts and decreases mitochondrial Ca2+ uptake and IP3R3-Grp75 interaction. Mfn2 overexpression increases ER-mitochondria contacts and the VAPB-PTPIP51 tethering pair interaction, supporting Mfn2 as a positive regulator of ER-mitochondrial tethering in vivo. Mfn2 conditional KO and overexpression mice; electron microscopy for ultrastructural quantification of ER-mitochondria contacts; biochemical fractionation; Co-immunoprecipitation of IP3R3-Grp75 and VAPB-PTPIP51 Journal of cell science High 34110411
2023 PGAM5 phosphatase interacts with MFN2 in a stress-sensitive manner and dephosphorylates MFN2 to protect it from ubiquitination and degradation, thereby promoting mitochondrial fusion. Phosphorylation of MFN2 enhances fission and degradation, while dephosphorylation enhances fusion. Drosophila genetic epistasis places Marf (MFN2 ortholog) and dPGAM5 in the same biological pathway. Co-immunoprecipitation of PGAM5-MFN2; phosphorylation and ubiquitination assays; mitochondrial morphology imaging; Drosophila genetic epistasis Cell reports High 37498743
2016 Drosophila Clu promotes VCP/p97-dependent Marf (MFN2 ortholog) degradation in the context of Parkin-mediated mitophagy; Clu binds VCP in vivo, and overexpression of Clu destabilizes Marf in vitro. This degradation step is required for progression of mitophagy. Drosophila genetic epistasis (clu, PINK1, parkin mutants); in vivo Co-IP of Clu-VCP; in vitro Marf degradation assay; confocal imaging of mitochondrial clearance Human molecular genetics Medium 26931463
2018 Parkin-dependent ubiquitination of Mfn2 at a specific site is required for ER-mitochondria tethering. In Parkin-deficient cells and patient fibroblasts, ER-mitochondria tethering is decreased. A non-ubiquitinatable Mfn2 mutant fails to restore ER-mitochondria physical and functional interaction. Co-immunoprecipitation; Parkin-deficient cells and parkin mutant human fibroblasts; non-ubiquitinatable Mfn2 mutant rescue experiments; Drosophila PD model behavioral rescue with synthetic ER-mitochondria linker Pharmacological research High 30219582
2017 MFN2 suppresses mTORC2/Akt signaling by directly interacting with mTORC2 through its HR1 domain. MFN2 knockout in cancer cells elevates mTORC2 activity and promotes AktS473 phosphorylation-mediated cancer growth and metastasis. CRISPR/Cas9 MFN2 knockout in MCF7 and A549 cells; Co-immunoprecipitation of MFN2-mTORC2; domain mapping (HR1 fragment); xenograft tumor model; signaling analysis Scientific reports Medium 28176801
2013 Endogenous Mfn2 inhibits cell proliferation by acting as an effector of Ras, inhibiting the Ras-Raf-ERK signaling pathway. The N-terminal fragment (aa 1-264) interacts with Raf-1, while the C-terminal fragment (aa 265-757) interacts with Ras to inhibit proliferation through distinct mechanisms. Mfn2 knockdown in BJAB cells and Mfn2 KO MEFs; reintroduction of Mfn2 fragments; Co-immunoprecipitation of N-term Mfn2 with Raf-1 and C-term Mfn2 with Ras; proliferation assays FASEB journal Medium 24081906
2014 Mfn2 physically contacts melanosomes through fibrillar bridges in pigment cells, and Mfn2 knockdown significantly reduces mitochondria-melanosome connections. Mfn2 loss prevents OA1-stimulated melanogenesis, linking Mfn2-dependent contacts to secretory organelle biogenesis. Electron tomography of mitochondria-melanosome contacts; Mfn2 knockdown; immunolocalization of Mfn2 at contact sites; melanogenesis assays Current biology Medium 24485836
2022 MFN2 physically interacts with PFK1 (phosphofructokinase 1) through its C-terminus, promoting PFK1 ubiquitin-proteasome dependent degradation by facilitating the association between PFK1 and E3 ligase TRIM21. MFN2 downregulation by mechanical stretch stabilizes PFK1, shifts metabolism toward glycolysis, and promotes VSMC proliferation/migration. Co-immunoprecipitation, pull-down, surface plasmon resonance, mutagenesis of MFN2 C-terminus; metabolomics; VSMC stretch model; vein graft mouse model Circulation research High 35450439
2021 VCP cofactor UBXN1 facilitates MFN2 removal from the outer mitochondrial membrane during PRKN-dependent mitophagy. Loss of UBXN1 impairs MFN2 extraction, leading to accumulation of para-mitochondrial MFN2 blobs and impaired PRKN translocation to depolarized mitochondria. UBXN1 knockout cells; Co-immunoprecipitation of UBXN1-PRKN (UBX domain dependent); mitochondrial fractionation; mitophagy flux assays; confocal and super-resolution imaging of MFN2 blobs Autophagy Medium 33966597
2021 Vps13D functions upstream of Marf/MFN2 in a conserved pathway regulating mitochondria-ER contact sites; vps13d mutants accumulate elevated Marf/MFN2 levels, and loss of marf/MFN2 suppresses vps13d mutant phenotypes including enlarged mitochondria-ER contacts and autophagy defects. Drosophila genetic epistasis (vmp1, vps13d, marf double/triple mutants); human cell VPS13D knockdown and MFN2 rescue; electron microscopy; autophagy assays Current biology Medium 34019822
2022 MFN1 and MFN2 promote clustering between mitochondria and peroxisomes; MFNs are enriched at the mitochondria-peroxisome interface, and a truncated MFN2 lacking the transmembrane region inhibits peroxisome-mitochondria tethering. Proximity labeling (BioID) with peroxisomal proteins; overexpression of MFNs; confocal microscopy of co-clustering; dominant-negative truncated MFN2 expression Communications biology Medium 35523862
2022 MFN2-stabilized MAMs increase in lifetime and stability during ER stress. MFN2 knockdown blunts mitochondrial Ca2+ uptake during ER stress, switches mitochondrial F1FO-ATPase into reverse mode, and strongly reduces ATP supply to the ER during ER stress. Structured illumination super-resolution microscopy of MAMs; MFN2 knockdown; mitochondrial Ca2+ measurements; OXPHOS and ATP assays during ER stress induction Frontiers in cell and developmental biology Medium 36158213
2022 In Drosophila, MARF (MFN2 ortholog) knockdown in heart tubes increases mitochondrial heterogeneity and induces cardiomyopathy, rescued by human MFN1 or MFN2, demonstrating functional homology. Reactive oxygen species mediate the cardiomyopathy in mitochondrial fusion-defective cardiomyocytes; SOD1 expression prevents the phenotype. Drosophila heart tube-specific RNAi of MARF; live imaging; human MFN1/MFN2 rescue; transgenic SOD1 overexpression; cardiomyocyte morphometric analysis Circulation research Medium 21148429
2014 In excitotoxicity, Mfn2 expression is downregulated via MEF2 transcription factor degradation. Mfn2 reduction causes mitochondrial dysfunction, altered calcium homeostasis, enhanced Bax translocation to mitochondria, and delayed neuronal death. MEF2 regulates basal Mfn2 expression in neurons. In vitro and in vivo excitotoxicity models; siRNA knockdown of Mfn2; MEF2 knockdown and overexpression; measurement of MEF2 binding to Mfn2 promoter; mitochondrial membrane potential and Bax translocation assays The EMBO journal Medium 25147362
2020 Mfn2 physically interacts with PERK in podocytes; high-glucose conditions decrease Mfn2-PERK interaction, and Mfn2 silencing activates the PERK pathway, causing MAM reduction, mitochondrial dysfunction, and increased apoptosis. Mfn2 overexpression inhibits PERK activation and is anti-apoptotic, and PERK inhibition does not affect Mfn2 levels, placing Mfn2 upstream of PERK. Co-immunoprecipitation of Mfn2-PERK; Mfn2 siRNA knockdown and overexpression in podocytes; PERK inhibitor treatment; mitochondrial morphology and MAM quantification; apoptosis assays Frontiers in cell and developmental biology Medium 34988075
2022 The CMT2A-associated MFN2 mutant R364W causes mitochondrial hyperfusion due to enhanced DRP1 ubiquitylation and proteasomal degradation by MITOL/MARCHF5. MITOL preferentially ubiquitylates wild-type MFN2 over R364W-MFN2, making the ligase more available for DRP1 multi-monoubiquitylation and degradation. Co-immunoprecipitation of MITOL with WT vs. R364W MFN2; ubiquitylation assays; proteasome inhibitor treatment; DRP1 degradation assays; mitochondrial morphology imaging Journal of cell science Medium 34870686
2023 LRRK2 kinase phosphorylates MFN2 at Ser27 via LRRK2-MKK4/JNK signaling, promoting ubiquitination-mediated MFN2 degradation and subsequent mitochondrial fragmentation in renal tubular cells. Lrrk2-knockout mice show MFN2 accumulation and reduced AKI severity. LRRK2 overexpression and Lrrk2 knockout mouse model; phospho-MFN2-Ser27 detection; Co-IP; JNK pathway inhibitor studies; mitochondrial morphology and ROS measurements Redox biology Medium 37633049
2023 Mfn2 interacts with MFN1 in testes and with nuage-associated proteins (MIWI, DDX4, TDRKH, GASZ); MFN2 also interacts with MSY2 in polysome fractions to regulate translation of gamete-specific mRNAs such as Spata19 during spermatogenesis. MFN2 conditional knockout in postnatal germ cells causes male sterility. Co-immunoprecipitation of MFN2 with nuage proteins and MSY2; polysome fractionation; conditional Mfn2 KO in postnatal germ cells; Mfn1/Mfn2 double KO; translational activity assays Development (Cambridge, England) Medium 33674260
2021 Mfn2 ablation specifically in spermatogonia causes DNA oxidation and apoptosis in differentiating spermatogonia and spermatocytes, causing male infertility. MFN2 regulates spermatogenesis by modulating both mitochondrial and ER functions, a distinct mechanism from MFN1; MFN2 defects are rescued only by MFN2 targeted to either organelle, not by MFN1. Mfn2 conditional KO in germ cells; Mfn1 conditional KO; organelle-targeted Mfn2 rescue constructs; DNA oxidation and apoptosis assays Stem cell reports Medium 32330448
2024 MFN2 recruits α-tubulin acetyltransferase 1 (ATAT1) to sites of mitochondria-microtubule contact, promoting local α-tubulin acetylation. This activity is required for MFN2-dependent regulation of mitochondrial transport. CMT2A-associated MFN2 mutations R94W and T105M cannot properly release ATAT1 at these contact sites, linking this function to axonal degeneration. Live imaging of mitochondria-microtubule contacts; Co-immunoprecipitation of MFN2-ATAT1; MFN2 KO and CMT2A mutant expression; measurement of α-tubulin acetylation and mitochondrial motility in neurons iScience Medium 38883841
2024 Mfn2 forms a complex with Hsc70 at mitochondria-lipid droplet contact (MLC) sites; mitochondrion-localized Mfn2 interacts with LD-localized Hsc70, tethering mitochondria to lipid droplets and facilitating fatty acid transfer from LDs to mitochondria for β-oxidation. Prolonged lipid overload induces MFN2 acetylation at K243 and subsequent ubiquitin-proteasome degradation. Co-immunoprecipitation of Mfn2-Hsc70; electron microscopy of MLC sites; Mfn2 knockdown and overexpression; fatty acid transfer assays; acetylation site mapping; in vivo lipid overload model Advanced science Medium 38311582
2020 Defective Mfn2 variants associated with CMT2A (near HB1-HB2 hinge) show reduced GTP-dependent oligomerization in cis and impaired membrane fusion in vitro; addition of cytosolic extract or soluble Bax improves both nucleotide-dependent assembly and fusion, suggesting cytosolic factors can compensate for molecular defects of CMT2A variants. In vitro membrane fusion assay with reconstituted proteoliposomes; nucleotide-dependent assembly assays; addition of purified Bax or cytosol extract; Mfn2-null cell rescue for morphology Life science alliance High 32245838
2023 E3 ubiquitin ligase RBCK1 interacts with and polyubiquitylates MFN2, promoting its proteasomal degradation under ferroptotic stress in pancreatic cancer cells, leading to decreased mitochondrial ROS production and lipid peroxidation, thereby conferring ferroptosis resistance. Co-immunoprecipitation of RBCK1-MFN2; ubiquitylation assays; RBCK1 knockdown/depletion; xenograft mouse model; ROS and lipid peroxidation measurements Free radical biology & medicine Medium 38763208
2022 MFN2 physically interacts with Rab21 (in its GTP-loaded form); through this EGFR-Rab21-MFN2 axis, endocytosed EGFR is docked to mitochondria and dephosphorylated by OMM-resident phosphatase PTPRJ, suppressing EGFR signaling and ccRCC progression. Bio-layer interferometry and Co-immunoprecipitation of MFN2-Rab21; Co-IP of EGFR-Rab21-MFN2; mass spectrometry; kidney-specific Mfn2 knockout mouse model; xenograft assays Cancer communications Medium 37378422
2023 Mfn2 downregulation in microglia causes mitochondrial fusion-fission imbalance, triggering release of mitochondrial DNA into the cytoplasm, which activates the cGAS-STING signaling pathway and aggravates neuroinflammation after spinal cord injury. Microglial Sting knockout mouse model; Mfn2 siRNA knockdown in microglia; cytosolic mtDNA quantification; cGAS-STING pathway activation assays (TBK1, IRF3 phosphorylation); nanoparticle delivery of MFN2 agonist Advanced science Medium 38009491
2019 E2F1 transcription factor directly binds the MFN2 promoter and increases endogenous MFN2 expression; E2F1 and SP1 form a complex on the MFN2 promoter during S-phase. E2F1-driven MFN2 expression modulates mitochondrial fusion and mitophagy. E2F1 overexpression; chromatin immunoprecipitation (ChIP) for E2F1 and SP1 on MFN2 promoter; Co-IP of E2F1-SP1; MFN2 mRNA and protein measurement; mitophagy and mitochondrial morphology assays The FEBS journal Medium 31276298
2023 Mfn2 physically interacts with IP3R3 in pulmonary arterial smooth muscle cells; this interaction mediates mitochondrial Ca2+ transport via MAMs. Mfn2 overexpression reduces IP3R3 expression, decreases excessive mitochondrial Ca2+ transport, and restores mitochondrial integrity, suppressing PASMCs proliferation. Co-immunoprecipitation of Mfn2-IP3R3; Mfn2 overexpression and silencing; IP3R3 inhibition; mitochondrial Ca2+ measurements; MCT-induced PAH rat model Journal of translational medicine Medium 40128893
2021 USP2 (deubiquitinating enzyme) interacts with MFN2 and stabilizes it through deubiquitination, thereby preventing mitochondrial dysfunction in cardiac hypertrophy. MFN2 knockdown neutralizes the protective effect of USP2 overexpression. Co-immunoprecipitation of USP2-MFN2; deubiquitination assay; USP2 overexpression and MFN2 siRNA rescue experiments; in vitro and in vivo cardiac hypertrophy models Molecular and cellular endocrinology Medium 37100191
2024 MORN4 directly binds MFN2 and promotes phosphorylation of MFN2-S442 through ROCK2 kinase, mediating beneficial mitophagy through mitochondrial dynamics. SPC promotes the MORN4-MFN2 interaction. Co-immunoprecipitation of MORN4-MFN2; phospho-MFN2-S442 measurement; ROCK2 kinase assays; MORN4 knockdown mouse MI model; confocal mitophagy assays Free radical biology & medicine Low 36682578
2020 Mul1 E3 ubiquitin ligase binds MFN2 and promotes its ubiquitination and degradation in the context of cerebral ischemia/reperfusion injury; ginsenoside CK reduces the Mul1-MFN2 binding affinity, thereby preserving MFN2 protein levels and mitochondrial dynamics. Co-immunoprecipitation of Mul1-Mfn2; ubiquitination assay; pharmacological reduction of Mul1-Mfn2 affinity; in vitro OGD/reperfusion and in vivo MCAO/reperfusion models Journal of ginseng research Low 37252276
2022 MFN2 stabilizes mitochondria-ER contact sites; the R364W-MFN2 CMT2A mutant alters ER-mitochondria association at MAM junctions, predisposes mitochondria to rapid fission upon mild stress, and perturbs inter-organellar calcium homeostasis. Confocal and proximity ligation assays for MAM contacts; mitochondrial Ca2+ and ER Ca2+ measurements; stress-induced fission assays in cells expressing WT vs. R364W-MFN2 Biology of the cell Low 35924634
2024 Endogenous MFN2 interactome (identified by CRISPR-Cas9 HA-tagging) includes RAB5C (endosomal modulator of mitochondrial homeostasis) and SLC27A2 (fatty acid transporter, relevant to autophagy) as novel validated partners, in addition to known ER and mitochondrial partners, with interactors regulated by nutrient deprivation. CRISPR-Cas9 endogenous HA-tagging of MFN2; HA affinity isolation followed by mass spectrometry; validation of RAB5C and SLC27A2 interactions; functional follow-up for autophagy Autophagy Medium 39675054
2011 A MFN2 missense mutation (D210V) causes multiple mitochondrial DNA deletions in skeletal muscle, establishing that impaired mitochondrial fusion due to MFN2 dysfunction leads to inability to repair stress-induced mitochondrial DNA damage, and that MFN2 is required for mtDNA stability. Genetic identification of MFN2 D210V mutation; detection of multiple mtDNA deletions in patient skeletal muscle; fibroblast mitochondrial network fragmentation and respiratory chain deficiency; mtDNA damage repair assay Brain : a journal of neurology Medium 22189565
2020 Mfn2 overexpression promotes ROS-dependent PINK1/Parkin-pathway mitophagy in nucleus pulposus cells, and Mfn2 overexpression protects against oxidative stress-induced autophagic flux impairment, mitochondrial dysfunction, and apoptosis. Autophagy inhibition blocks these protective effects. Mfn2 KD and OE in rat nucleus pulposus cells; PINK1/Parkin pathway assays; autophagic flux assays; chloroquine inhibition; adenoviral Mfn2 injection in rodent disc degeneration model Osteoarthritis and cartilage Low 31926268
2022 Rab26 interacts with MFN2 and affects MFN2 transport to mitochondria; Rab26 deficiency reduces MFN2 levels in mitochondria, decreasing mitochondrial ROS and ATP production and impairing macrophage phagocytosis. Co-immunoprecipitation of Rab26-MFN2; Rab26 knockout macrophages; MFN2 mitochondrial localization assay; MFN2 siRNA; phagocytosis and ROS/ATP measurements; in vivo Rab26 KO ARDS model The FEBS journal Medium 37060270

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. The Journal of cell biology 2109 12527753
2013 Mfn2 modulates the UPR and mitochondrial function via repression of PERK. The EMBO journal 387 23921556
2016 Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. The EMBO journal 333 27334614
2006 MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain : a journal of neurology 320 16714318
2020 The AMPK-MFN2 axis regulates MAM dynamics and autophagy induced by energy stresses. Autophagy 259 32249716
2017 Mfn2 is critical for brown adipose tissue thermogenic function. The EMBO journal 230 28348166
2019 Targeting mitochondrial dynamics by regulating Mfn2 for therapeutic intervention in diabetic cardiomyopathy. Theranostics 205 31281507
2018 MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A. Science (New York, N.Y.) 203 29674596
2011 The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy 'plus' phenotype. Brain : a journal of neurology 193 22189565
2018 Regulation of ER-mitochondria contacts by Parkin via Mfn2. Pharmacological research 180 30219582
2014 Mitochondria and melanosomes establish physical contacts modulated by Mfn2 and involved in organelle biogenesis. Current biology : CB 142 24485836
2017 MFN2 suppresses cancer progression through inhibition of mTORC2/Akt signaling. Scientific reports 112 28176801
2015 MFN2-related neuropathies: Clinical features, molecular pathogenesis and therapeutic perspectives. Journal of the neurological sciences 110 26143526
2010 MARF and Opa1 control mitochondrial and cardiac function in Drosophila. Circulation research 108 21148429
2020 Ferroptosis mediated by the interaction between Mfn2 and IREα promotes arsenic-induced nonalcoholic steatohepatitis. Environmental research 103 32593899
2023 Isorhapontigenin Attenuates Cardiac Microvascular Injury in Diabetes via the Inhibition of Mitochondria-Associated Ferroptosis Through PRDX2-MFN2-ACSL4 Pathways. Diabetes 100 36367849
2013 Role of mitofusin 2 (Mfn2) in controlling cellular proliferation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 98 24081906
2022 Overexpression of MFN2 alleviates sorafenib-induced cardiomyocyte necroptosis via the MAM-CaMKIIδ pathway in vitro and in vivo. Theranostics 93 35154486
2014 Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death. The EMBO journal 93 25147362
2021 Mfn2 Regulates High Glucose-Induced MAMs Dysfunction and Apoptosis in Podocytes via PERK Pathway. Frontiers in cell and developmental biology 92 34988075
2022 Mfn2-mediated mitochondrial fusion promotes autophagy and suppresses ovarian cancer progression by reducing ROS through AMPK/mTOR/ERK signaling. Cellular and molecular life sciences : CMLS 91 36308626
2018 Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy. Oncology reports 87 29436693
2022 The Role of Impaired Mitochondrial Dynamics in MFN2-Mediated Pathology. Frontiers in cell and developmental biology 84 35399520
2013 Anti-tumor effects of Mfn2 in gastric cancer. International journal of molecular sciences 82 23797661
2023 Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8+ T cell metabolic fitness and function in tumors. Science immunology 79 37738362
2023 Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy. Journal of neuroinflammation 77 36765376
2016 Melatonin prevents adverse myocardial infarction remodeling via Notch1/Mfn2 pathway. Free radical biology & medicine 72 27387769
2019 MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. International journal of biological sciences 70 31754334
2014 Dysregulation of Mfn2 and Drp-1 proteins in heart failure. Canadian journal of physiology and pharmacology 70 24905188
2020 Mfn2 is involved in intervertebral disc degeneration through autophagy modulation. Osteoarthritis and cartilage 69 31926268
2020 MFN2 contributes to metabolic disorders and inflammation in the aging of rat chondrocytes and osteoarthritis. Osteoarthritis and cartilage 67 32416221
2022 Paeonol protects against doxorubicin-induced cardiotoxicity by promoting Mfn2-mediated mitochondrial fusion through activating the PKCε-Stat3 pathway. Journal of advanced research 66 35842187
2021 The role of Mfn2 in the structure and function of endoplasmic reticulum-mitochondrial tethering in vivo. Journal of cell science 66 34110411
2023 Cytoplasmic Escape of Mitochondrial DNA Mediated by Mfn2 Downregulation Promotes Microglial Activation via cGas-Sting Axis in Spinal Cord Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 62 38009491
2021 Mitochondrial Fusion Protein Mfn2 and Its Role in Heart Failure. Frontiers in molecular biosciences 61 34026850
2021 Mfn2 localization in the ER is necessary for its bioenergetic function and neuritic development. EMBO reports 61 34296790
2022 MFN2-driven mitochondria-to-nucleus tethering allows a non-canonical nuclear entry pathway of the mitochondrial pyruvate dehydrogenase complex. Molecular cell 58 35245450
2024 Mfn2/Hsc70 Complex Mediates the Formation of Mitochondria-Lipid Droplets Membrane Contact and Regulates Myocardial Lipid Metabolism. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 56 38311582
2024 Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling. Journal of neuroinflammation 55 38566081
2020 Mfn2 Ablation in the Adult Mouse Hippocampus and Cortex Causes Neuronal Death. Cells 54 31947766
2023 Decreased MFN2 activates the cGAS-STING pathway in diabetic myocardial ischaemia-reperfusion by triggering the release of mitochondrial DNA. Cell communication and signaling : CCS 53 37537600
2018 MFN2-associated lipomatosis: Clinical spectrum and impact on adipose tissue. Journal of clinical lipidology 53 30158064
2019 PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK-CREB-Mfn2-mitophagy signaling pathway. Journal of cellular physiology 50 31654396
2015 Mfn2 Affects Embryo Development via Mitochondrial Dysfunction and Apoptosis. PloS one 49 25978725
2022 MFN2 mediates ER-mitochondrial coupling during ER stress through specialized stable contact sites. Frontiers in cell and developmental biology 46 36158213
2022 The MFN1 and MFN2 mitofusins promote clustering between mitochondria and peroxisomes. Communications biology 44 35523862
2016 Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation. Human molecular genetics 39 26931463
2023 Role of mitochondrial fusion proteins MFN2 and OPA1 on lung cellular senescence in chronic obstructive pulmonary disease. Respiratory research 38 38110986
2022 MFN2 Prevents Neointimal Hyperplasia in Vein Grafts via Destabilizing PFK1. Circulation research 38 35450439
2023 PGAM5 is an MFN2 phosphatase that plays an essential role in the regulation of mitochondrial dynamics. Cell reports 37 37498743
2021 MicroRNA-17-5p Promotes Cardiac Hypertrophy by Targeting Mfn2 to Inhibit Autophagy. Cardiovascular toxicology 37 34120306
2022 Ginsenoside compound K protects against cerebral ischemia/reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy. Journal of ginseng research 36 37252276
2020 MFN2 Plays a Distinct Role from MFN1 in Regulating Spermatogonial Differentiation. Stem cell reports 34 32330448
2020 Mycobacterium tuberculosis infection up-regulates MFN2 expression to promote NLRP3 inflammasome formation. The Journal of biological chemistry 34 33454007
2021 VCP/p97 cofactor UBXN1/SAKS1 regulates mitophagy by modulating MFN2 removal from mitochondria. Autophagy 32 33966597
2017 Enhancing Mitofusin/Marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies. Neurobiology of aging 32 28324764
2021 Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease. Current biology : CB 31 34019822
2022 Mitofusins Mfn1 and Mfn2 Are Required to Preserve Glucose- but Not Incretin-Stimulated β-Cell Connectivity and Insulin Secretion. Diabetes 28 35472764
2022 TRPV4 interacts with MFN2 and facilitates endoplasmic reticulum-mitochondrial contact points for Ca2+-buffering. Life sciences 25 36283455
2023 MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR. Cancer communications (London, England) 24 37378422
2022 Clinical and genetic features of a cohort of patients with MFN2-related neuropathy. Scientific reports 24 35418194
2021 USP30 protects against oxygen-glucose deprivation/reperfusion induced mitochondrial fragmentation and ubiquitination and degradation of MFN2. Aging 24 33609088
2023 LRRK2 aggravates kidney injury through promoting MFN2 degradation and abnormal mitochondrial integrity. Redox biology 23 37633049
2022 MITOL-mediated DRP1 ubiquitylation and degradation promotes mitochondrial hyperfusion in a CMT2A-linked MFN2 mutant. Journal of cell science 23 34870686
2019 E2F1 activates MFN2 expression by binding to the promoter and decreases mitochondrial fission and mitophagy in HeLa cells. The FEBS journal 23 31276298
2020 The distinctive role of tau and amyloid beta in mitochondrial dysfunction through alteration in Mfn2 and Drp1 mRNA Levels: A comparative study in Drosophila melanogaster. Gene 22 32525045
2019 Mfn2 inhibits proliferation and cell-cycle in Hela cells via Ras-NF-κB signal pathway. Cancer cell international 22 31384172
2016 MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients. Journal of the peripheral nervous system : JPNS 22 26801520
2022 LncRNA NEAT1 ameliorate ischemic stroke via promoting Mfn2 expression through binding to Nova and activates Sirt3. Metabolic brain disease 21 35067795
2022 Lanthanum decreased VAPB-PTPP51, BAP31-FIS1, and MFN2-MFN1 expression of mitochondria-associated membranes and induced abnormal autophagy in rat hippocampus. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 20 35090998
2015 MFN2 deletion of exons 7 and 8: founder mutation in the UK population. Journal of the peripheral nervous system : JPNS 19 26114802
2010 HSG/Mfn2 gene polymorphism and essential hypertension: a case-control association study in Chinese. Journal of atherosclerosis and thrombosis 19 20940517
2020 Mammalian STE20‑like kinase 1 regulates pancreatic cancer cell survival and migration through Mfn2‑mediated mitophagy. Molecular medicine reports 18 32377725
2025 Mfn2 regulates calcium homeostasis and suppresses PASMCs proliferation via interaction with IP3R3 to mitigate pulmonary arterial hypertension. Journal of translational medicine 17 40128893
2024 MFN2 coordinates mitochondria motility with α-tubulin acetylation and this regulation is disrupted in CMT2A. iScience 17 38883841
2023 Metformin Collaborates with PINK1/Mfn2 Overexpression to Prevent Cardiac Injury by Improving Mitochondrial Function. Biology 17 37106782
2023 Down-regulation of the mitochondrial fusion protein Opa1/Mfn2 promotes cardiomyocyte hypertrophy in Su5416/hypoxia-induced pulmonary hypertension rats. Archives of biochemistry and biophysics 17 37696382
2023 Combined RNA interference and gene replacement therapy targeting MFN2 as proof of principle for the treatment of Charcot-Marie-Tooth type 2A. Cellular and molecular life sciences : CMLS 17 38007410
2023 Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin-induced myocardial injury. Cancer innovation 16 38089747
2022 CircHIPK3 Regulates Vascular Smooth Muscle Cell Calcification Via the miR-106a-5p/MFN2 Axis. Journal of cardiovascular translational research 16 35467292
2021 Marf-mediated mitochondrial fusion is imperative for the development and functioning of indirect flight muscles (IFMs) in drosophila. Experimental cell research 16 33450208
2021 Low abundance of Mfn2 protein correlates with reduced mitochondria-SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 33749943
2024 Ginsenoside Rb1 ameliorates lipotoxicity-induced myocardial injury in diabetes mellitus by regulating Mfn2. European journal of pharmacology 15 38677536
2024 E3 ubiquitin ligase RBCK1 confers ferroptosis resistance in pancreatic cancer by facilitating MFN2 degradation. Free radical biology & medicine 15 38763208
2022 CMT2A-linked mitochondrial hyperfusion-driving mutant MFN2 perturbs ER-mitochondrial associations and Ca2+ homeostasis. Biology of the cell 15 35924634
2022 Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication. Frontiers in immunology 15 35958608
2021 MFN2 interacts with nuage-associated proteins and is essential for male germ cell development by controlling mRNA fate during spermatogenesis. Development (Cambridge, England) 15 33674260
2020 Defective nucleotide-dependent assembly and membrane fusion in Mfn2 CMT2A variants improved by Bax. Life science alliance 15 32245838
2013 Ethambutol toxicity exacerbating the phenotype of CMT2A2. Muscle & nerve 15 23733358
2023 MORN4 protects cardiomyocytes against ischemic injury via MFN2-mediated mitochondrial dynamics and mitophagy. Free radical biology & medicine 14 36682578
2023 Crosstalk between Mfn2-mediated mitochondria associated membranes disorder and autophagy induced by molybdenum and cadmium in sheep heart. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 14 36803920
2024 DIAPH1-MFN2 interaction decreases the endoplasmic reticulum-mitochondrial distance and promotes cardiac injury following myocardial ischemia. Nature communications 12 38368414
2024 Mfn2 regulates mitochondria and mitochondria-associated endoplasmic reticulum membrane function in neurodegeneration induced by repeated sevoflurane exposure. Experimental neurology 12 38704082
2023 Rab26 promotes macrophage phagocytosis through regulation of MFN2 trafficking to mitochondria. The FEBS journal 12 37060270
2023 Angiotensin II-induced calcium overload affects mitochondrial functions in cardiac hypertrophy by targeting the USP2/MFN2 axis. Molecular and cellular endocrinology 12 37100191
2022 MiR-195 promotes pancreatic β-cell dedifferentiation by targeting Mfn2 and impairing Pi3k/Akt signaling in type 2 diabetes. Obesity (Silver Spring, Md.) 12 35088561
2019 Sphingosine kinase 1 overexpression induces MFN2 fragmentation and alters mitochondrial matrix Ca2+ handling in HeLa cells. Biochimica et biophysica acta. Molecular cell research 12 31220477
2023 AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway. Hepatobiliary & pancreatic diseases international : HBPD INT 11 36966125
2024 Endogenous interactomes of MFN1 and MFN2 provide novel insights into interorganelle communication and autophagy. Autophagy 10 39675054
2021 The Genotype and Phenotype Features in a Large Chinese MFN2 Mutation Cohort. Frontiers in neurology 10 34721278

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