The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MFN2  -  mitofusin 2

Homo sapiens

Synonyms: CMT2A, CMT2A2, CPRP1, HSG, KIAA0214, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of MFN2


High impact information on MFN2

  • Moreover, mutations in the mitochondrial fusion genes Mitofusin-2 and OPA1 lead to the peripheral neuropathy Charcot-Marie-Tooth type 2A and dominant optic atrophy [3].
  • These studies indicate that orally administered HSG can survive passage in the gastrointestinal tract in an immunologically active form, and that the oral administration of immunoglobulins with specific reactivities has potential for the prevention or treatment of gastrointestinal infections [4].
  • We examined the pharmacokinetics and immunological activity of human serum immunoglobulins (HSG) possessing anti-rota-virus activity which were orally administered to three children with primary immunodeficiency syndromes and prolonged gastrointestinal excretion of rotavirus [4].
  • Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis [5].
  • Mitofusin-2 (Mfn2) is a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells and mutations in the Mfn2 gene cause Charcot-Marie-Tooth neuropathy type 2A [6].

Chemical compound and disease context of MFN2


Biological context of MFN2

  • METHODS: The authors performed a standardized neuromuscular and nerve conduction examination, genotyped known CMT loci, and analyzed the MFN2 gene by direct sequencing in three pedigrees and 10 additional probands affected by axonal CMT [12].
  • Upon staurosporine-stimulated cell death, activated Bax is recruited to the Mfn2-containing puncta; however, Bax activation and cytochrome c release are inhibited in the presence of the dominant active mutants of Mfn2 [13].
  • Mitochondrial fusion is stimulated dramatically within heterokaryons expressing this mutant, demonstrating that hydrolysis is not requisite for the fusion event, and supporting a role for Mfn2 as a signaling GTPase [13].
  • The potential for regulation of human Mfn2 gene expression in vivo is largely unknown [14].
  • The mitofusins (Mfn1 and Mfn2) are homologs of the Drosophila protein fuzzy onion (Fzo) that associate with mitochondria and alter mitochondrial morphology when expressed by transient transfection in tissue culture cells [15].

Anatomical context of MFN2

  • INTERPRETATION: MFN2 is a mitochondrial membrane protein that was recently reported to cause axonal CMT type 2A [1].
  • Overexpression of MARCH-V promoted the formation of long tubular mitochondria in a manner that depends on MFN2 activity [16].
  • This is the first evidence that Mfn2 is a signaling GTPase regulating mitochondrial fusion and that the nucleotide-dependent activation of Mfn2 concomitantly protects the organelle from permeability transition [13].
  • Obesity-induced Mfn2 deficiency in rat skeletal muscle was also associated with a decrease in the subunits of complexes I, II, III and V [6].
  • In vitro experiments revealed an inhibitory effect of TNFalpha or interleukin-6 on Mfn2 expression in cultured cells [14].

Associations of MFN2 with chemical compounds

  • The percentage changes in MFN2 mRNA were positively correlated with the percentage change in glucose oxidation during the clamp (glucose oxidation percent (%) change=0.3 MFN2 mRNA percent (%) change+153.2; R2=0.61, p<0.001) [2].
  • Estrogen stimulation also induced long cytoplasmic extensions, filopodia formation, and abnormal outgrowths in both HSG and HSY cells [7].
  • Vitamin K3 induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 or HSG cells [17].
  • The cytotoxic activity of CGA against human oral tumor cells (HSC-2, HSG) was completely eliminated by lower concentrations of sodium ascorbate or NAC, whereas that of sodium ascorbate or NAC was only slightly reduced by CGA [18].
  • Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody) [8].

Enzymatic interactions of MFN2


Other interactions of MFN2

  • Mitochondrial fusion in higher eukaryotes requires at least two essential GTPases, Mitofusin 1 and Mitofusin 2 (Mfn2) [13].
  • BACKGROUND: Axonal neuropathy linked to the CMT2A locus was originally associated with a mutation in the KIF1B gene [12].
  • Surprisingly, Drp1 and Mfn2, but not other proteins implicated in the regulation of mitochondrial morphology, colocalize with Bax in these foci [5].
  • The PGC-1alpha/ERRalpha-mediated induction of Mfn2 suggests a role of these two factors in mitochondrial fusion [19].
  • The cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) and human gingival fibroblast cells (HGF) declined in the order of DBP >> bisDBP = TBP = TBP-OOH (2,4,6-tri-t-butyl-4-hydroperoxy-2,5-cyclohexadiene-1-one) [20].

Analytical, diagnostic and therapeutic context of MFN2


  1. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Züchner, S., De Jonghe, P., Jordanova, A., Claeys, K.G., Guergueltcheva, V., Cherninkova, S., Hamilton, S.R., Van Stavern, G., Krajewski, K.M., Stajich, J., Tournev, I., Verhoeven, K., Langerhorst, C.T., de Visser, M., Baas, F., Bird, T., Timmerman, V., Shy, M., Vance, J.M. Ann. Neurol. (2006) [Pubmed]
  2. Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity? Mingrone, G., Manco, M., Calvani, M., Castagneto, M., Naon, D., Zorzano, A. Diabetologia (2005) [Pubmed]
  3. Critical dependence of neurons on mitochondrial dynamics. Chen, H., Chan, D.C. Curr. Opin. Cell Biol. (2006) [Pubmed]
  4. Oral administration of human serum immunoglobulin in immunodeficient patients with viral gastroenteritis. A pharmacokinetic and functional analysis. Losonsky, G.A., Johnson, J.P., Winkelstein, J.A., Yolken, R.H. J. Clin. Invest. (1985) [Pubmed]
  5. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. Karbowski, M., Lee, Y.J., Gaume, B., Jeong, S.Y., Frank, S., Nechushtan, A., Santel, A., Fuller, M., Smith, C.L., Youle, R.J. J. Cell Biol. (2002) [Pubmed]
  6. The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Pich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., Zorzano, A. Hum. Mol. Genet. (2005) [Pubmed]
  7. Biological Role of Estrogen Receptor {beta} in Salivary Gland Adenocarcinoma Cells. Ohshiro, K., Rayala, S.K., Williams, M.D., Kumar, R., El-Naggar, A.K. Clin. Cancer Res. (2006) [Pubmed]
  8. Induction of apoptosis by dopamine in human oral tumor cell lines. Terasaka, H., Tamura, A., Takayama, F., Kashimata, M., Ohtomo, K., Machino, M., Fujisawa, S., Toguchi, M., Kanda, Y., Kunii, S., Kusama, K., Ishino, A., Watanabe, S., Satoh, K., Takano, H., Takahama, M., Sakagami, H. Anticancer Res. (2000) [Pubmed]
  9. Cellular proliferation and ras oncogene of p21 21,000 expression in relation to the intracellular cyclic adenosine 3':5'-monophosphate levels of a human salivary gland adenocarcinoma cell line in culture. Azuma, M., Yoshida, H., Kawamata, H., Yanagawa, T., Furumoto, N., Sato, M. Cancer Res. (1988) [Pubmed]
  10. Cytotoxicity, ROS-generation activity and radical-scavenging activity of curcumin and related compounds. Fujisawa, S., Atsumi, T., Ishihara, M., Kadoma, Y. Anticancer Res. (2004) [Pubmed]
  11. Cytotoxic activity of 5-benzoylimidazole and related compounds against human oral tumor cell lines. Terasawa, K., Sugita, Y., Yokoe, I., Fujisawa, S., Sakagami, H. Anticancer Res. (2001) [Pubmed]
  12. Clinical and electrophysiologic features of CMT2A with mutations in the mitofusin 2 gene. Lawson, V.H., Graham, B.V., Flanigan, K.M. Neurology (2005) [Pubmed]
  13. Activated mitofusin 2 signals mitochondrial fusion, interferes with Bax activation, and reduces susceptibility to radical induced depolarization. Neuspiel, M., Zunino, R., Gangaraju, S., Rippstein, P., McBride, H. J. Biol. Chem. (2005) [Pubmed]
  14. Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6. Bach, D., Naon, D., Pich, S., Soriano, F.X., Vega, N., Rieusset, J., Laville, M., Guillet, C., Boirie, Y., Wallberg-Henriksson, H., Manco, M., Calvani, M., Castagneto, M., Palacín, M., Mingrone, G., Zierath, J.R., Vidal, H., Zorzano, A. Diabetes (2005) [Pubmed]
  15. Control of mitochondrial morphology by a human mitofusin. Santel, A., Fuller, M.T. J. Cell. Sci. (2001) [Pubmed]
  16. MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. Nakamura, N., Kimura, Y., Tokuda, M., Honda, S., Hirose, S. EMBO Rep. (2006) [Pubmed]
  17. Cytotoxic activity of vitamins K1, K2 and K3 against human oral tumor cell lines. Okayasu, H., Ishihara, M., Satoh, K., Sakagami, H. Anticancer Res. (2001) [Pubmed]
  18. Interaction between chlorogenic acid and antioxidants. Jiang, Y., Satoh, K., Kusama, K., Watanabe, S., Sakagami, H. Anticancer Res. (2000) [Pubmed]
  19. Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. Cartoni, R., Léger, B., Hock, M.B., Praz, M., Crettenand, A., Pich, S., Ziltener, J.L., Luthi, F., Dériaz, O., Zorzano, A., Gobelet, C., Kralli, A., Russell, A.P. J. Physiol. (Lond.) (2005) [Pubmed]
  20. Radical production and cytotoxic activity of tert-butyl-substituted phenols. Saito, M., Atsumi, T., Satoh, K., Ishihara, M., Iwakura, I., Sakagami, H., Yokoe, I., Fujisawa, S. In vitro & molecular toxicology. (2001) [Pubmed]
  21. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. Rojo, M., Legros, F., Chateau, D., Lombès, A. J. Cell. Sci. (2002) [Pubmed]
  22. Intermediate-sized filaments and specific markers in a human salivary gland adenocarcinoma cell line and its nude mouse tumors. Sato, M., Hayashi, Y., Yanagawa, T., Yoshida, H., Yura, Y., Azuma, M., Ueno, A. Cancer Res. (1985) [Pubmed]
  23. Role of laminin-1 and TGF-beta 3 in acinar differentiation of a human submandibular gland cell line (HSG). Hoffman, M.P., Kibbey, M.C., Letterio, J.J., Kleinman, H.K. J. Cell. Sci. (1996) [Pubmed]
  24. Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p (CMT2A) and the clinical features of CMT2A. Saito, M., Hayashi, Y., Suzuki, T., Tanaka, H., Hozumi, I., Tsuji, S. Neurology (1997) [Pubmed]
WikiGenes - Universities