Affinage

MFN2

Mitofusin-2 · UniProt O95140

Length
757 aa
Mass
86.4 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MFN2 is a dynamin-family GTPase embedded in the outer mitochondrial membrane that functions as a master organelle tethering protein, mediating mitochondrial outer-membrane fusion through GTP-dependent homo- and heterotypic complexes with MFN1, while also tethering mitochondria to the ER, nuclear envelope, lipid droplets, peroxisomes, and melanosomes to coordinate interorganellar communication (PMID:12527753, PMID:34296790, PMID:35245450, PMID:38311582, PMID:35523862, PMID:24485836). ER-localized MFN2 interacts in trans with mitochondrial MFN1/2 to form mitochondria-associated ER membrane (MAM) contacts that facilitate IP3R/Grp75-dependent Ca²⁺ transfer from ER to mitochondria, sustaining oxidative phosphorylation, and this tethering function is regulated by Parkin-mediated ubiquitination, USP30 deubiquitination, PGAM5 dephosphorylation, and LRRK2-MKK4/JNK phosphorylation at Ser27, which collectively control MFN2 stability and the balance between fusion, fission, and mitophagy (PMID:34296790, PMID:34110411, PMID:30219582, PMID:37498743, PMID:37633049, PMID:38147294, PMID:35042405). Beyond its tethering roles, MFN2 directly suppresses PERK kinase activity at MAMs, recruits ATAT1 to promote α-tubulin acetylation for mitochondrial transport, and forms Hsc70-dependent contacts between mitochondria and lipid droplets that enable fatty acid transfer for β-oxidation (PMID:23921556, PMID:38883841, PMID:38311582). Mutations in MFN2 cause Charcot-Marie-Tooth disease type 2A (CMT2A), with disease-linked variants such as R94W, T105M, and R364W showing defects in GTPase-dependent cis-assembly, ATAT1 release, or MITOL interaction that impair fusion and axonal mitochondrial transport (PMID:32245838, PMID:38883841, PMID:34870686).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    The foundational question of how mammalian mitochondria fuse was answered by demonstrating that MFN1 and MFN2 are each essential and sufficient for mitochondrial outer-membrane fusion through homotypic and heterotypic complexes, establishing the mitofusin family as the core fusion machinery.

    Evidence Mfn1/Mfn2 KO MEFs with genetic rescue and Co-IP for complex formation

    PMID:12527753

    Open questions at the time
    • No structural model of the fusion-competent complex
    • Mechanism of lipid bilayer merger not resolved
    • Relative contribution of homo- vs heterotypic complexes in different tissues unknown
  2. 2010 High

    Functional conservation of MFN2 in cardiac tissue was established when Drosophila MARF cardiac knockdown caused cardiomyopathy rescued by human MFN2, with SOD1 epistasis identifying ROS as the downstream pathogenic mediator.

    Evidence Drosophila heart-specific RNAi rescued by human MFN2 and by SOD1 overexpression

    PMID:21148429

    Open questions at the time
    • Mechanism by which fusion loss elevates cardiac ROS not defined
    • Not tested in mammalian cardiac-specific knockout
  3. 2013 High

    MFN2 was found to have signaling functions beyond fusion: it directly interacts with and represses the ER stress kinase PERK, and separately inhibits Ras-Raf-ERK signaling through distinct N- and C-terminal domain interactions with Raf-1 and Ras, revealing MFN2 as a signaling scaffold.

    Evidence Co-IP of endogenous MFN2-PERK with PERK-siRNA epistasis rescue; Co-IP of MFN2 domain fragments with Ras/Raf-1 in KO MEFs

    PMID:23921556 PMID:24081906

    Open questions at the time
    • Structural basis of MFN2-PERK interaction unknown
    • Whether Ras and PERK interactions are simultaneous or competitive not tested
    • Ras-Raf interaction confirmed in limited cell types
  4. 2014 Medium

    MFN2 was shown to mediate interorganellar contacts beyond ER-mitochondria, localizing to mitochondria-melanosome interfaces where it maintains fibrillar tethers required for melanogenesis.

    Evidence Electron tomography with MFN2 siRNA in pigment cells; OA1 stimulation experiments

    PMID:24485836

    Open questions at the time
    • Identity of the melanosome-side tethering partner unknown
    • Not confirmed in human melanocytes
    • Whether this requires MFN2 GTPase activity not tested
  5. 2018 High

    The regulatory ubiquitination of MFN2 by Parkin was shown to be required not just for mitophagy but specifically for maintaining ER-mitochondria tethering, with non-ubiquitinatable MFN2 mutants failing to restore contacts in Parkin-deficient patient fibroblasts.

    Evidence Ubiquitination site mapping, non-ubiquitinatable MFN2 rescue in Parkin-deficient fibroblasts, Drosophila synthetic linker rescue

    PMID:30219582

    Open questions at the time
    • Specific ubiquitin chain type required for tethering vs. degradation not distinguished
    • Whether Parkin ubiquitination affects MFN2 conformation unknown
  6. 2020 High

    In vitro reconstitution with purified MFN2 revealed that nucleotide-dependent cis-assembly (not trans) is the critical step for membrane fusion, and CMT2A variants at the HB1-HB2 hinge are specifically defective in this step; cytosolic Bax masks variant defects, explaining why some CMT2A mutations show mild cellular phenotypes.

    Evidence Reconstituted fusion assay with purified CMT2A MFN2 variants; Bax rescue experiments

    PMID:32245838

    Open questions at the time
    • How Bax facilitates fusion mechanistically unclear
    • Whether all CMT2A variants share the cis-assembly defect not tested
    • No cryo-EM structure of the fusion intermediate
  7. 2020 High

    MFN2 was identified as an AMPK-interacting protein at MAMs that couples energy sensing to autophagy; MFN2 (but not MFN1) is required for MAM abundance and autophagy induction during energy stress.

    Evidence Reciprocal Co-IP of AMPK-MFN2; MFN2-null MEF rescue; EM quantification of MAMs; Seahorse metabolic analysis

    PMID:32249716

    Open questions at the time
    • Whether AMPK phosphorylates MFN2 directly at MAMs not determined
    • How MFN2 selectively maintains MAMs under energy stress mechanistically unclear
  8. 2021 High

    The dual-pool model of MFN2 function was refined: ER-localized MFN2 alone is sufficient to tether ER to mitochondria and enhance Ca²⁺ transfer and bioenergetics, while in vivo neuronal studies showed MFN2 stabilizes the VAPB-PTPIP51 and IP3R3-Grp75 tethering complexes at MAMs.

    Evidence Compartment-targeted MFN2 constructs in KO neurons; in vivo Mfn2 cKO/OE mice with EM, Ca²⁺ measurements, and tethering complex Co-IPs

    PMID:34110411 PMID:34296790

    Open questions at the time
    • How MFN2 stabilizes VAPB-PTPIP51 interaction mechanistically unknown
    • Whether ER-MFN2 uses the same GTPase cycle as mitochondrial MFN2 for tethering not established
  9. 2021 Medium

    A non-canonical role for MFN2 in male germ cell translational regulation was discovered: MFN2 interacts with nuage components and the RNA-binding protein MSY2 to regulate polysome-associated translation of gamete-specific mRNAs, with conditional KO causing male sterility.

    Evidence Co-IP of MFN2 with MIWI, DDX4, TDRKH, GASZ, MSY2; conditional Mfn2 KO mouse; polysome fractionation

    PMID:33674260

    Open questions at the time
    • Whether MFN2 directly binds RNA not tested
    • Mechanism of MFN2 entry into polysome fractions unknown
    • Not replicated in independent labs
  10. 2022 High

    MFN2 was shown to mediate mitochondria-nuclear envelope tethering, enabling a non-canonical, NPC-independent import of mitochondrial pyruvate dehydrogenase complex into the nucleus through lamin A, linking mitochondrial metabolism to histone acetylation.

    Evidence MFN2 KD/OE with confocal and EM of mito-nuclear contacts; NPC blockade; lamin A Co-IP with PDC

    PMID:35245450

    Open questions at the time
    • Mechanism of PDC transfer through the nuclear envelope not resolved at molecular level
    • Whether other mitochondrial proteins use this route unknown
    • Quantitative contribution to nuclear acetyl-CoA pools not established
  11. 2022 High

    The mitophagy mechanism was further refined: Parkin selectively ubiquitinates MFN2 near PINK1/phospho-ubiquitin foci on depolarized mitochondria using a His433-dependent acyl transfer mechanism, with MFN2 being a kinetically preferred Parkin substrate; downstream, VCP cofactor UBXN1 extracts ubiquitinated MFN2 to enable Parkin recruitment and mitophagic flux.

    Evidence In vitro ubiquitination with isolated mitochondria; RING2 His433 mutagenesis; proximity ligation; UBXN1 KO mitophagy assays

    PMID:33966597 PMID:35042405

    Open questions at the time
    • Whether MFN2 extraction is rate-limiting for mitophagy in vivo unknown
    • Other VCP cofactors that may participate not fully mapped
  12. 2022 Medium

    CMT2A-linked R364W mutation was shown to cause mitochondrial hyperfusion (not fragmentation) by redirecting MITOL E3 ligase from MFN2 to DRP1, causing DRP1 degradation and fission blockade, revealing that disease mutations can act through gain-of-function redistribution of ubiquitin ligase activity.

    Evidence Co-IP of MITOL with WT vs R364W MFN2; DRP1 ubiquitination and stability assays; MITOL knockdown rescue

    PMID:34870686

    Open questions at the time
    • Whether other CMT2A mutations similarly redirect MITOL not tested
    • Single lab finding
    • Mechanism of weakened R364W-MITOL interaction not structurally defined
  13. 2022 Medium

    MFN2's tethering repertoire was expanded to include peroxisomes and endosomes: MFN1/2 cluster at mitochondria-peroxisome contacts, and MFN2 interacts with GTP-Rab21 to dock endocytosed EGFR to mitochondria for dephosphorylation by PTPRJ, suppressing EGFR signaling.

    Evidence BioID proximity labeling at peroxisomes; dominant-negative MFN2; Co-IP and BLI of MFN2-Rab21; kidney-specific MFN2 KO mouse

    PMID:35523862 PMID:37378422

    Open questions at the time
    • Whether MFN2 is a direct tethering component at peroxisomes or indirect not resolved
    • Rab21-MFN2 interaction domain not mapped
    • EGFR docking mechanism in non-renal tissues not examined
  14. 2022 High

    PGAM5 was identified as a MFN2 phosphatase that dephosphorylates MFN2 to protect it from ubiquitination and degradation, maintaining the fusion-competent state; phospho-MFN2 promotes fission and degradation, establishing a phosphorylation switch controlling fusion-fission balance.

    Evidence Co-IP; phosphorylation and ubiquitination assays; Drosophila genetic epistasis of Marf and dPGAM5

    PMID:37498743

    Open questions at the time
    • Specific phosphorylation sites targeted by PGAM5 not fully mapped
    • How stress signals switch PGAM5 activity toward MFN2 vs DRP1 not defined
  15. 2023 High

    MFN2 was established as a key metabolic regulator in T cell immunity: interaction with SERCA2 at MAMs balances mitochondrial Ca²⁺ influx for metabolism while preventing Ca²⁺ overload and apoptosis, and conditional MFN2 loss in CD8⁺ T cells impairs anti-tumor immunity.

    Evidence Co-IP of MFN2-SERCA2; conditional KO in CD8⁺ T cells; tumor models; Ca²⁺ and metabolic profiling

    PMID:37738362

    Open questions at the time
    • Whether MFN2-SERCA2 interaction is direct or complex-mediated not resolved
    • Structural basis of interaction unknown
  16. 2023 Medium

    USP30 was identified as the deubiquitinase that opposes Parkin-mediated MFN2 ubiquitination; LRRK2 was shown to phosphorylate MFN2 at Ser27 via MKK4/JNK to trigger ubiquitination and degradation, establishing two additional regulatory inputs into MFN2 stability control.

    Evidence USP30 inhibitor and OE with ubiquitination assays; LRRK2 KO with phospho-Ser27 detection and in vivo AKI model

    PMID:37633049 PMID:38147294

    Open questions at the time
    • Whether USP30 and LRRK2 pathways converge on the same ubiquitin sites unknown
    • Ser27 phosphorylation not validated by phosphoproteomics in independent studies
  17. 2024 High

    MFN2 was shown to form Hsc70-dependent tethering complexes at mitochondria-lipid droplet contact sites, directly facilitating fatty acid transfer for β-oxidation; acetylation at K243 under lipid overload triggers MFN2 proteasomal degradation and contact disruption.

    Evidence Co-IP of MFN2-Hsc70 at MLC sites; EM; K243 acetylation mutagenesis; in vivo cardiomyocyte models

    PMID:38311582

    Open questions at the time
    • Acetyltransferase responsible for K243 modification not identified
    • Whether Hsc70 acts as a tether or chaperone at the contact not distinguished
  18. 2024 Medium

    MFN2 was found to recruit ATAT1 to mitochondria-microtubule contacts to promote local α-tubulin acetylation required for mitochondrial transport; CMT2A mutations R94W and T105M fail to release ATAT1, linking disrupted tubulin acetylation to axonal transport defects in disease.

    Evidence Co-IP of MFN2-ATAT1; live imaging of contact sites; CMT2A mutant comparison; transport assays

    PMID:38883841

    Open questions at the time
    • Whether ATAT1 recruitment requires MFN2 GTPase activity not tested
    • Mechanism of ATAT1 release at contact sites not defined
    • Single lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive functional characterization, the high-resolution structural mechanism of MFN2-mediated membrane fusion (the lipid merger step), the logic by which MFN2 selectively engages distinct organelle partners, and the integration of its multiple phosphorylation and ubiquitination inputs into a unified regulatory code remain unresolved.
  • No high-resolution structure of full-length human MFN2 in a membrane context
  • No unified model of how MFN2 selects among ER, LD, peroxisome, melanosome, and nuclear envelope partners
  • Quantitative contribution of each post-translational modification to MFN2 activity in vivo not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 2 GO:0098772 molecular function regulator activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005739 mitochondrion 7 GO:0005783 endoplasmic reticulum 3 GO:0005635 nuclear envelope 1 GO:0005811 lipid droplet 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-9612973 Autophagy 5 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-1430728 Metabolism 1
Partners
ATAT1HSPA8MFN1PERKPGAM5PRKNSERCA2USP30
Complex memberships
MFN1-MFN2 heterotypic fusion complexMFN2-Hsc70 mitochondria-lipid droplet tetherPINK1-Parkin-MFN2 mitophagy complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Mfn1 and Mfn2 are essential mediators of mitochondrial fusion; they form homotypic (Mfn1-Mfn1, Mfn2-Mfn2) and heterotypic (Mfn1-Mfn2) complexes, and loss of either protein causes severe mitochondrial fragmentation due to a block in fusion. Homotypic complexes are each independently functional for fusion. Loss of fusion also causes a subset of mitochondria to lose membrane potential. Mfn1/Mfn2 knockout mouse embryonic fibroblasts, genetic rescue with individual Mfn constructs, Co-IP for complex formation, live imaging of mitochondrial morphology The Journal of cell biology High 12527753
2013 Mfn2 physically interacts with the ER stress kinase PERK and acts as an upstream repressor of PERK activity; Mfn2 ablation causes sustained basal PERK activation, which in turn drives elevated ROS, altered mitochondrial calcium, and abnormal mitochondrial morphology. Co-IP of endogenous Mfn2-PERK in Mfn2-ablated and control cells; PERK siRNA epistasis experiments; calcium and ROS measurements in Mfn2-null MEFs The EMBO journal High 23921556
2018 Parkin-dependent ubiquitination of Mfn2 at a specific site is required for ER-mitochondria tethering; a non-ubiquitinatable Mfn2 mutant fails to restore physical and functional ER-mitochondria contacts, and Parkin-deficient cells show reduced ER-mitochondria juxtaposition. Co-IP/ubiquitination site mapping; non-ubiquitinatable Mfn2 mutant rescue in Parkin-deficient human fibroblasts; ER-mitochondria contact quantification; in vivo Drosophila locomotor rescue with synthetic ER-mitochondria linker Pharmacological research High 30219582
2014 Mfn2 localizes to mitochondria-melanosome contact sites and its knockdown significantly reduces the interorganellar fibrillar bridges between these two organelles, impairing melanogenesis; OA1 stimulation increases contacts requiring Mfn2. Electron tomography; siRNA knockdown of Mfn2 in pigment cells; quantification of organelle contact frequency; pharmacological inhibition of mitochondrial ATP synthesis Current biology : CB Medium 24485836
2015 The homozygous MFN2 p.R707W substitution impairs homotypic Mfn2-Mfn2 protein interactions required for normal activity and causes mitochondria to aggregate perinuclearly in patient fibroblasts. Functional studies in patient fibroblasts (homotypic interaction assays, mitochondrial morphology imaging) from individuals with homozygous MFN2 R707W Human molecular genetics Medium 26085578
2020 AMPK directly interacts with and translocates to MFN2-containing MAM sites under energy stress; MFN2 (but not MFN1) is required for normal MAM abundance and autophagy induction in response to energy deprivation, linking the energy-sensing AMPK pathway to MFN2-dependent MAM dynamics. Direct Co-IP of AMPK and MFN2; MFN2-null MEF rescue experiments; MAM quantification by EM; Seahorse metabolic analysis; live-cell imaging of AMPK translocation Autophagy High 32249716
2021 In vivo, Mfn2 promotes ER-mitochondria close contacts (MERCs) in hippocampal neurons; Mfn2 conditional KO reduces and Mfn2 overexpression increases MERC number and mitochondrial Ca2+ uptake; Mfn2 also stabilizes the VAPB-PTPIP51 tethering pair interaction and the IP3R3-Grp75 complex. Mfn2 cKO and overexpression mouse models; electron microscopy ultrastructural quantification; biochemical MAM fractionation; mitochondrial Ca2+ measurements; Co-IP of VAPB-PTPIP51 and IP3R3-Grp75 Journal of cell science High 34110411
2021 ER-localized Mfn2 (not mitochondria-localized Mfn2) is sufficient to enhance mitochondrial metabolism by tethering ER and mitochondria via ER-Mfn2 interaction with mitochondrial Mfn1/2, enabling Ca2+ transfer from ER to mitochondria; this ER-localized pool is also required for proper neuritic outgrowth. Compartment-targeted Mfn2 constructs (ER-Mfn2 vs. mito-Mfn2); Mfn2 KO neuron rescue; artificial ER-mito tether rescue; Ca2+ transfer assays; mitochondrial bioenergetics (OCR) EMBO reports High 34296790
2022 MFN2 mediates mitochondria-to-nuclear envelope tethering; mitochondria cluster around the nucleus via MFN2-enriched contact points on the nuclear envelope, enabling a non-canonical (NPC-independent) nuclear import of mitochondrial pyruvate dehydrogenase complex (PDC) that crosses through lamin A and facilitates histone acetylation. MFN2 knockdown/overexpression; confocal and EM imaging of mitochondria-nuclear contacts; proximity ligation; NPC blockade experiments; lamin A co-IP with PDC; nPDC quantification Molecular cell High 35245450
2022 PGAM5 is a phosphatase for MFN2; PGAM5 dephosphorylates MFN2 to protect it from ubiquitination and proteasomal degradation, thereby promoting mitochondrial fusion. Phosphorylated MFN2 promotes fission and degradation, while dephosphorylated MFN2 promotes fusion. PGAM5 interacts with MFN2 and DRP1 in a stress-sensitive manner. Co-IP of PGAM5 with MFN2 and DRP1; phosphorylation and ubiquitination assays; mitochondrial morphology analysis; Drosophila genetic epistasis (Marf and dPGAM5 in same pathway) Cell reports High 37498743
2022 MFN2 acts as a GTPase whose nucleotide-dependent assembly in cis (not trans) is critical for membrane fusion; CMT2A-associated variants near the HB1-HB2 hinge show reduced nucleotide-dependent cis assembly and fusion deficiency in vitro, which is rescued by cytosolic Bax, indicating cytosolic factors mask disease-variant defects in cells. In vitro reconstituted fusion assay with purified Mfn2 CMT2A variants; nucleotide-dependent assembly assays; Bax addition rescue; cell morphology rescue as comparison Life science alliance High 32245838
2022 MFN2 interacts with the small GTPase Rab21 in its GTP-loaded form; through the EGFR-Rab21-MFN2 axis, endocytosed EGFR is docked to mitochondria and dephosphorylated by the OMM-residing phosphatase PTPRJ, suppressing EGFR signaling and ccRCC progression. Co-IP, bio-layer interferometry, mass spectrometry; kidney-specific MFN2 KO mouse with EGFR pathway activation phenotype; immunofluorescence colocalization; RNA-seq Cancer communications Medium 37378422
2022 MFN1 and MFN2 promote physical clustering between mitochondria and peroxisomes; MFNs are enriched at mitochondria-peroxisome interfaces, overexpression induces co-clustering, and a transmembrane-domain-truncated MFN2 inhibits peroxisome-mitochondria tethering. Proximity labeling (BioID) with peroxisomal bait; confocal co-imaging; truncated MFN2 dominant-negative expression; quantification of contact sites Communications biology Medium 35523862
2022 Mfn2 is selectively ubiquitinated by Parkin in proximity to PINK1/phospho-ubiquitin foci on depolarized mitochondria; His433 in Parkin's RING2 domain catalyzes acyl transfer, and Mfn2 is a kinetically preferred Parkin substrate in vitro, with preferential localization near PINK1 driving efficient ubiquitination. In vitro ubiquitination assay with isolated mitochondria; proximity-ligation assay for Mfn2-PINK1-pUb colocalization; Parkin RING2 His433 mutagenesis; mitophagy functional assay Open biology High 35042405
2021 The VCP cofactor UBXN1/SAKS1 facilitates MFN2 removal from the outer mitochondrial membrane downstream of PINK1; loss of UBXN1 traps MFN2 in para-mitochondrial 'blobs', impairs PRKN recruitment, and blocks mitophagic flux. UBXN1 KO cell lines; MFN2 ubiquitination and degradation assays; Parkin translocation imaging; mitophagy flux assays; Co-IP of UBXN1-PRKN Autophagy Medium 33966597
2022 A CMT2A-linked MFN2 mutation (R364W) causes mitochondrial hyperfusion by redirecting MITOL (MARCHF5) E3 ligase activity away from MFN2 and toward DRP1; R364W-MFN2 has weaker MITOL interaction, leaving MITOL free to polyubiquitinate and proteasomally degrade DRP1, thereby blocking fission. Co-IP of MITOL with WT vs. R364W MFN2; DRP1 ubiquitination and stability assays; MITOL knockdown rescue; proteasome inhibitor experiments; mitochondrial morphology quantification Journal of cell science Medium 34870686
2013 Endogenous Mfn2 exerts antiproliferative effects by acting as an effector of Ras, inhibiting the Ras-Raf-ERK pathway; the N-terminal domain (aa 1–264) of Mfn2 interacts with Raf-1, while the C-terminal domain (aa 265–757) interacts with Ras, and these interactions are responsible for proliferation suppression. Mfn2 knockdown in B-cell lymphoma cells and Mfn2-KO MEFs; N- and C-terminal Mfn2 domain overexpression; Co-IP of Mfn2 fragments with Raf-1 and Ras; ERK pathway western blot FASEB journal Medium 24081906
2021 MFN2 interacts with nuage-associated proteins (MIWI, DDX4, TDRKH, GASZ) and with the RNA-binding protein MSY2 in testis; conditional mutation of Mfn2 in postnatal germ cells causes male sterility, and MFN2-MSY2 interaction regulates translational activity of gamete-specific mRNAs (e.g., Spata19) in polysome fractions. Co-IP of MFN2 with nuage proteins; conditional Mfn2 KO mouse; polysome fractionation showing MFN2 enrichment; double Mfn1/Mfn2 conditional KO phenotype Development Medium 33674260
2023 MFN2 physically interacts with SERCA2 on the ER; in tumor-infiltrating CD8+ T cells, this MFN2-SERCA2 interaction enhances mitochondria-ER contacts, facilitates mitochondrial Ca2+ influx for efficient mitochondrial metabolism, and simultaneously allows SERCA2 to retrieve excess ER Ca2+ preventing mitochondrial Ca2+ overload and apoptosis. Co-IP of MFN2 with SERCA2; Mfn2 conditional KO in CD8+ T cells (KO + tumor models); mitochondrial Ca2+ measurements; metabolic profiling; cancer immunotherapy efficacy experiments Science immunology High 37738362
2024 Mfn2 and LD-localized Hsc70 form a complex at mitochondria-lipid droplet membrane contact (MLC) sites that tethers mitochondria to lipid droplets, facilitating fatty acid transfer from LDs to mitochondria for β-oxidation; lipid overload reduces Mfn2 via ubiquitin-proteasome degradation following acetylation at K243, disrupting MLC and causing lipid accumulation. Co-IP of Mfn2 with Hsc70 at MLC sites; electron microscopy visualization of MLC; Mfn2 overexpression/knockdown in cardiomyocytes + in vivo; fatty acid transfer assays; K243 acetylation site mutagenesis; ubiquitin-proteasome pathway assays Advanced science High 38311582
2024 MFN2 recruits α-tubulin acetyltransferase 1 (ATAT1) to sites of mitochondria-microtubule contacts, promoting local α-tubulin acetylation; this is required for MFN2-dependent mitochondrial transport regulation. CMT2A-linked mutations R94W and T105M fail to release ATAT1 at mitochondria-microtubule contact sites, implicating disrupted tubulin acetylation in axonal degeneration. Co-IP of MFN2 with ATAT1; live imaging of mitochondria-microtubule contacts; immunofluorescence of acetylated tubulin at contact sites; CMT2A mutant (R94W, T105M) comparison; mitochondrial transport assays iScience Medium 38883841
2023 Mfn2 downregulation in microglia leads to mitochondrial fission imbalance and release of mitochondrial DNA into the cytoplasm, which activates the cGAS-STING signaling pathway, driving neuroinflammation after spinal cord injury. Mfn2 knockdown in microglial cells; cytosolic mtDNA quantification; cGAS-STING pathway activation assays; Sting microglial KO mice; in vivo SCI mouse model Advanced science Medium 38009491
2023 USP30 deubiquitinates MFN2 on the outer mitochondrial membrane, protecting it from degradation; inhibition of USP30 allows Parkin-mediated MFN2 ubiquitination, which separates damaged mitochondria from the healthy network and promotes mitophagy to clear damaged mitochondria after SAH. USP30 inhibitor (MF094) and overexpression in neuronal SAH models; MFN2 ubiquitination assays; mitophagy flux measurements; apoptosis assays; in vivo SAH mouse model neurological scoring Translational stroke research Medium 38147294
2023 LRRK2 phosphorylates MFN2 at Ser27 via a LRRK2-MKK4/JNK-dependent cascade, triggering ubiquitination-mediated MFN2 degradation, mitochondrial fragmentation, and increased ROS in renal tubular cells; LRRK2 loss accumulates MFN2 and protects against ischemia/reperfusion kidney injury. LRRK2 overexpression/KO in human PTC cells and Lrrk2−/− mice; phospho-MFN2 Ser27 detection; ubiquitination assays; MFN2 protein stability analysis; mitochondrial morphology and ROS quantification; in vivo AKI model Redox biology Medium 37633049
2010 Drosophila MARF (ortholog of human MFN1/MFN2) is required for mitochondrial fusion in cardiomyocytes; cardiac-specific MARF knockdown causes mitochondrial heterogeneity, heart tube dilation, and contractile impairment, all of which are rescued by human MFN1 or MFN2, establishing functional homology; superoxide dismutase 1 overexpression prevents the cardiomyopathy, implicating ROS as the key mediator. Drosophila heart-tube-specific RNAi (tincΔ4Gal4); rescue with human MFN1/MFN2; SOD1 transgenic rescue; live imaging of heart contractility; mitochondrial morphometry Circulation research High 21148429
2016 Mfn2 is required for PINK1/Parkin-mediated mitophagy; VCP-dependent Marf (MFN2 ortholog) degradation is promoted by the Drosophila protein Clueless, which binds VCP in vivo, and Marf accumulation blocks efficient mitophagic clearance of damaged mitochondria. Drosophila clueless mutant and overexpression; Parkin/VCP co-localization imaging; in vitro VCP-dependent Marf degradation assay; genetic epistasis with parkin, vcp, and clueless Human molecular genetics Medium 26931463
2021 Mfn2 interacts with PERK at MAM junctions; high-glucose conditions decrease Mfn2 expression and reduce Mfn2-PERK interaction in podocytes, leading to MAM reduction, mitochondrial dysfunction, PERK pathway activation, and increased apoptosis; PERK phosphorylation inhibition improves mitochondrial function but does not affect Mfn2 levels, placing Mfn2 upstream of PERK. Co-IP of Mfn2 with PERK in podocytes; Mfn2 siRNA and overexpression; PERK inhibitor epistasis; MAM quantification by EM; mitochondrial functional assays; human DKD tissue analysis Frontiers in cell and developmental biology Medium 34988075
2024 E3 ubiquitin ligase RBCK1 interacts with and polyubiquitinates MFN2, targeting it for proteasomal degradation under ferroptotic stress; MFN2 degradation decreases mitochondrial ROS production and lipid peroxidation, conferring ferroptosis resistance in pancreatic cancer cells. Co-IP of RBCK1 with MFN2; ubiquitination assay; RBCK1 KO xenograft mouse model; mitochondrial ROS measurement; lipid peroxidation assays Free radical biology & medicine Medium 38763208
2023 Co-IP confirmed that Mfn2 interacts with IRE1α at ER-mitochondria contact sites (MAMs); this interaction promotes production of 5-HETE (a lipid peroxidation product) and ferroptosis in arsenic-induced NASH. Co-IP of Mfn2 with IRE1α; Mfn2 siRNA knockdown; IRE1α inhibitor experiments; 5-HETE quantification; ferroptosis hallmark assays Environmental research Medium 32593899
2025 Mfn2 physically interacts with IP3R3 at MAMs; Mfn2 overexpression reduces IP3R3 expression and decreases mitochondrial Ca2+ transport in PASMCs, while Mfn2 silencing exacerbates ER stress and increases mitochondrial Ca2+ uptake, thereby suppressing PASMC proliferation and pulmonary vascular remodeling. Immunoprecipitation assay confirming Mfn2-IP3R3 interaction; Mfn2 overexpression and siRNA in PASMCs; mitochondrial Ca2+ measurement; MCT-induced PAH rat model Journal of translational medicine Medium 40128893
2022 MFN2 interacts with TRPV4 channels; TRPV4 expression modulates mitochondrial morphology and Ca2+ levels, and ER-mitochondria contact points are inversely regulated with mitochondrial Ca2+ levels in a TRPV4-dependent manner involving MFN2. Co-IP of TRPV4 with MFN1/MFN2 in CHO-K1 stable cells and mouse brain mitochondria; pharmacological TRPV4 modulation; quantitative EM analysis of ~55,000 mitochondrial particles and ~125,000 ER-mito contacts; mitochondrial Ca2+ imaging Life sciences Medium 36283455
2020 MEF2 transcription factor regulates basal Mfn2 expression in neurons; excitotoxicity-dependent MEF2 degradation causes Mfn2 downregulation, leading to a delayed phase of mitochondrial fragmentation, mitochondrial dysfunction, altered calcium homeostasis, enhanced Bax translocation, and neuronal death. In vitro cortical culture and in vivo excitotoxicity models; MEF2 siRNA and reporter assays; Mfn2 expression time-course; Drp1 inhibitor epistasis; calcium imaging; Bax translocation assays The EMBO journal Medium 25147362
2023 MFN2 overexpression suppresses mitochondrial translocation of ACSL4, thereby inhibiting mitochondria-associated ferroptosis in cardiac microvascular endothelial cells in diabetes. MFN2 overexpression in endothelial cells; ACSL4 mitochondrial localization by fractionation and confocal imaging; lipid peroxidation and iron assays in db/db mice Diabetes Medium 36367849

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 2085 12527753
2013 Mfn2 modulates the UPR and mitochondrial function via repression of PERK. The EMBO journal 383 23921556
2016 Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. The EMBO journal 322 27334614
2006 MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain : a journal of neurology 317 16714318
2020 The AMPK-MFN2 axis regulates MAM dynamics and autophagy induced by energy stresses. Autophagy 249 32249716
2019 Targeting mitochondrial dynamics by regulating Mfn2 for therapeutic intervention in diabetic cardiomyopathy. Theranostics 197 31281507
2018 Regulation of ER-mitochondria contacts by Parkin via Mfn2. Pharmacological research 179 30219582
2014 Mitochondria and melanosomes establish physical contacts modulated by Mfn2 and involved in organelle biogenesis. Current biology : CB 140 24485836
2015 MFN2-related neuropathies: Clinical features, molecular pathogenesis and therapeutic perspectives. Journal of the neurological sciences 108 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 102 32593899
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
2023 Isorhapontigenin Attenuates Cardiac Microvascular Injury in Diabetes via the Inhibition of Mitochondria-Associated Ferroptosis Through PRDX2-MFN2-ACSL4 Pathways. Diabetes 96 36367849
2017 Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis. EMBO reports 91 28539390
2014 Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death. The EMBO journal 90 25147362
2022 Overexpression of MFN2 alleviates sorafenib-induced cardiomyocyte necroptosis via the MAM-CaMKIIδ pathway in vitro and in vivo. Theranostics 89 35154486
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 87 36308626
2018 Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy. Oncology reports 87 29436693
2021 Mfn2 Regulates High Glucose-Induced MAMs Dysfunction and Apoptosis in Podocytes via PERK Pathway. Frontiers in cell and developmental biology 83 34988075
2013 Anti-tumor effects of Mfn2 in gastric cancer. International journal of molecular sciences 82 23797661
2022 The Role of Impaired Mitochondrial Dynamics in MFN2-Mediated Pathology. Frontiers in cell and developmental biology 77 35399520
2023 Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8+ T cell metabolic fitness and function in tumors. Science immunology 75 37738362
2016 Melatonin prevents adverse myocardial infarction remodeling via Notch1/Mfn2 pathway. Free radical biology & medicine 72 27387769
2023 Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy. Journal of neuroinflammation 71 36765376
2022 Resveratrol Reestablishes Mitochondrial Quality Control in Myocardial Ischemia/Reperfusion Injury through Sirt1/Sirt3-Mfn2-Parkin-PGC-1α Pathway. Molecules (Basel, Switzerland) 69 36080311
2017 Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression. eLife 69 28414270
2014 Dysregulation of Mfn2 and Drp-1 proteins in heart failure. Canadian journal of physiology and pharmacology 69 24905188
2019 MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. International journal of biological sciences 68 31754334
2020 MFN2 contributes to metabolic disorders and inflammation in the aging of rat chondrocytes and osteoarthritis. Osteoarthritis and cartilage 65 32416221
2015 Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy. Human molecular genetics 65 26085578
2022 Paeonol protects against doxorubicin-induced cardiotoxicity by promoting Mfn2-mediated mitochondrial fusion through activating the PKCε-Stat3 pathway. Journal of advanced research 62 35842187
2021 The role of Mfn2 in the structure and function of endoplasmic reticulum-mitochondrial tethering in vivo. Journal of cell science 60 34110411
2021 Mfn2 localization in the ER is necessary for its bioenergetic function and neuritic development. EMBO reports 59 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
2019 MiR-195-5p Promotes Cardiomyocyte Hypertrophy by Targeting MFN2 and FBXW7. BioMed research international 58 31341888
2021 Mitochondrial Fusion Protein Mfn2 and Its Role in Heart Failure. Frontiers in molecular biosciences 57 34026850
2020 Mfn2 Ablation in the Adult Mouse Hippocampus and Cortex Causes Neuronal Death. Cells 53 31947766
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) 52 38009491
2018 MFN2-associated lipomatosis: Clinical spectrum and impact on adipose tissue. Journal of clinical lipidology 51 30158064
2024 Mfn2/Hsc70 Complex Mediates the Formation of Mitochondria-Lipid Droplets Membrane Contact and Regulates Myocardial Lipid Metabolism. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 50 38311582
2019 PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK-CREB-Mfn2-mitophagy signaling pathway. Journal of cellular physiology 48 31654396
2015 Mfn2 Affects Embryo Development via Mitochondrial Dysfunction and Apoptosis. PloS one 48 25978725
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 46 37537600
2024 Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling. Journal of neuroinflammation 45 38566081
2022 The MFN1 and MFN2 mitofusins promote clustering between mitochondria and peroxisomes. Communications biology 40 35523862
2016 Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation. Human molecular genetics 38 26931463
2014 Tumour necrosis factor-α promotes liver ischaemia-reperfusion injury through the PGC-1α/Mfn2 pathway. Journal of cellular and molecular medicine 38 24898700
2021 MicroRNA-17-5p Promotes Cardiac Hypertrophy by Targeting Mfn2 to Inhibit Autophagy. Cardiovascular toxicology 37 34120306
2023 PGAM5 is an MFN2 phosphatase that plays an essential role in the regulation of mitochondrial dynamics. Cell reports 35 37498743
2023 Role of mitochondrial fusion proteins MFN2 and OPA1 on lung cellular senescence in chronic obstructive pulmonary disease. Respiratory research 35 38110986
2017 Clinical and genetic diversities of Charcot-Marie-Tooth disease with MFN2 mutations in a large case study. Journal of the peripheral nervous system : JPNS 34 28660751
2020 Mycobacterium tuberculosis infection up-regulates MFN2 expression to promote NLRP3 inflammasome formation. The Journal of biological chemistry 33 33454007
2018 Low expression of MFN2 is associated with early unexplained miscarriage by regulating autophagy of trophoblast cells. Placenta 33 30316324
2022 Ginsenoside compound K protects against cerebral ischemia/reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy. Journal of ginseng research 32 37252276
2017 Enhancing Mitofusin/Marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies. Neurobiology of aging 32 28324764
2015 Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model. PloS one 32 26327438
2023 Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH. Translational stroke research 31 38147294
2021 VCP/p97 cofactor UBXN1/SAKS1 regulates mitophagy by modulating MFN2 removal from mitochondria. Autophagy 30 33966597
2018 Deficiency of parkin suppresses melanoma tumor development and metastasis through inhibition of MFN2 ubiquitination. Cancer letters 30 29981809
2018 RETRACTED: MicroRNA-497 promotes proliferation and inhibits apoptosis of cardiomyocytes through the downregulation of Mfn2 in a mouse model of myocardial ischemia-reperfusion injury. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 29852387
2022 TRPV4 interacts with MFN2 and facilitates endoplasmic reticulum-mitochondrial contact points for Ca2+-buffering. Life sciences 24 36283455
2021 USP30 protects against oxygen-glucose deprivation/reperfusion induced mitochondrial fragmentation and ubiquitination and degradation of MFN2. Aging 24 33609088
2020 Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions. Environmental science and pollution research international 24 33165700
2022 Selective localization of Mfn2 near PINK1 enables its preferential ubiquitination by Parkin on mitochondria. Open biology 23 35042405
2022 Clinical and genetic features of a cohort of patients with MFN2-related neuropathy. Scientific reports 23 35418194
2014 Mutation analysis of MFN2, GJB1, MPZ and PMP22 in Italian patients with axonal Charcot-Marie-Tooth disease. Neuromolecular medicine 23 24819634
2023 Trophoblast Stem-Cell-Derived Exosomes Alleviate Cardiotoxicity of Doxorubicin via Improving Mfn2-Mediated Mitochondrial Fusion. Cardiovascular toxicology 22 36609664
2022 MITOL-mediated DRP1 ubiquitylation and degradation promotes mitochondrial hyperfusion in a CMT2A-linked MFN2 mutant. Journal of cell science 22 34870686
2016 MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients. Journal of the peripheral nervous system : JPNS 22 26801520
2023 MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR. Cancer communications (London, England) 21 37378422
2022 LncRNA NEAT1 ameliorate ischemic stroke via promoting Mfn2 expression through binding to Nova and activates Sirt3. Metabolic brain disease 21 35067795
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 21 32525045
2020 Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia-Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling. Frontiers in cell and developmental biology 21 33195281
2016 MiR-106b-mediated Mfn2 suppression is critical for PKM2 induced mitochondrial fusion. American journal of cancer research 21 27822413
2023 LRRK2 aggravates kidney injury through promoting MFN2 degradation and abnormal mitochondrial integrity. Redox biology 20 37633049
2018 A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 20 29361379
2018 Betaine enhances the cellular survival via mitochondrial fusion and fission factors, MFN2 and DRP1. Animal cells and systems 20 30460110
2015 A cohort study of Han Chinese MFN2-related Charcot-Marie-Tooth 2A. Journal of the neurological sciences 20 26382835
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
2023 Metformin Collaborates with PINK1/Mfn2 Overexpression to Prevent Cardiac Injury by Improving Mitochondrial Function. Biology 17 37106782
2025 Mfn2 regulates calcium homeostasis and suppresses PASMCs proliferation via interaction with IP3R3 to mitigate pulmonary arterial hypertension. Journal of translational medicine 16 40128893
2024 MFN2 coordinates mitochondria motility with α-tubulin acetylation and this regulation is disrupted in CMT2A. iScience 16 38883841
2023 Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin-induced myocardial injury. Cancer innovation 16 38089747
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
2018 Low MFN2 expression related to ageing in granulosa cells is associated with assisted reproductive technology outcome. Reproductive biomedicine online 16 30593438
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 15 37696382
2022 CircHIPK3 Regulates Vascular Smooth Muscle Cell Calcification Via the miR-106a-5p/MFN2 Axis. Journal of cardiovascular translational research 15 35467292
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 Marf-mediated mitochondrial fusion is imperative for the development and functioning of indirect flight muscles (IFMs) in drosophila. Experimental cell research 15 33450208
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
2024 Ginsenoside Rb1 ameliorates lipotoxicity-induced myocardial injury in diabetes mellitus by regulating Mfn2. European journal of pharmacology 14 38677536
2024 E3 ubiquitin ligase RBCK1 confers ferroptosis resistance in pancreatic cancer by facilitating MFN2 degradation. Free radical biology & medicine 14 38763208
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
2022 Melatonin attenuates spatial learning and memory dysfunction in developing rats by suppressing isoflurane-induced endoplasmic reticulum stress via the SIRT1/Mfn2/PERK signaling pathway. Heliyon 14 36091956
2020 Defective nucleotide-dependent assembly and membrane fusion in Mfn2 CMT2A variants improved by Bax. Life science alliance 14 32245838
2013 Ethambutol toxicity exacerbating the phenotype of CMT2A2. Muscle & nerve 14 23733358
2023 Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the HAND2-AS1/miR-17-5p/Mfn2 axis. BMC cardiovascular disorders 13 36882677
2022 CMT2A-linked mitochondrial hyperfusion-driving mutant MFN2 perturbs ER-mitochondrial associations and Ca2+ homeostasis. Biology of the cell 13 35924634