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MFN1  -  mitofusin 1

Homo sapiens

Synonyms: FLJ20693, Fzo homolog, Mitofusin-1, Transmembrane GTPase MFN1, hfzo1, ...
 
 
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High impact information on MFN1

 

Biological context of MFN1

  • 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 [6].
  • Mitofusin (Mfn) proteins regulate the biogenesis and maintenance of the mitochondrial network, and when inactivated, cause a failure in the mitochondrial architecture and decreases in oxidative capacity and glucose oxidation [7].
  • On the outer membrane, the fuzzy onions/mitofusin proteins form complexes in trans that mediate homotypic physical interactions between adjacent mitochondria and are likely directly involved in outer membrane fusion [8].
  • Conversely, a protein variant carrying a point mutation in the G2 motif of the Mfn1 GTPase domain acted as a dominant negative: overexpression of Mfn1T109A resulted in fragmentation of mitochondria [9].
  • In addition, recent reports shed new light on the physiological importance of Mitofusin function suggesting a role in mitochondrial metabolism, apoptosis as well as cellular signalling [10].
 

Anatomical context of MFN1

  • Forced expression of Mfn1 in cultured cells caused formation of characteristic networks of mitochondria [9].
  • The approximately 450 kDa complex contained oligomerized Mfn1 from distinct apposing membranes (docking complex), whereas the approximately 250 kDa complex was composed of Mfn1 present on the same membrane or in the membrane-solubilized state (cis complex) [5].
  • What is the biological significance of the two mitofusin proteins present in the outer mitochondrial membrane of mammalian cells [11]?
  • The hfzo genes were expressed mainly in the brain and in muscle that are postmitotic, but not in the pancreas [12].
 

Associations of MFN1 with chemical compounds

 

Other interactions of MFN1

 

Analytical, diagnostic and therapeutic context of MFN1

  • Two human Fzo-homologs, mitofusins Mfn1 and Mfn2, are shown by RT-PCR and western blot to be ubiquitous mitochondrial proteins [14].

References

  1. Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. Barsoum, M.J., Yuan, H., Gerencser, A.A., Liot, G., Kushnareva, Y., Gräber, S., Kovacs, I., Lee, W.D., Waggoner, J., Cui, J., White, A.D., Bossy, B., Martinou, J.C., Youle, R.J., Lipton, S.A., Ellisman, M.H., Perkins, G.A., Bossy-Wetzel, E. EMBO J. (2006) [Pubmed]
  2. Novel transmembrane GTPase of non-small cell lung cancer identified by mRNA differential display. Chung, J.G., Yeh, K.T., Wu, S.L., Hsu, N.Y., Chen, G.W., Yeh, Y.W., Ho, H.C. Cancer Res. (2001) [Pubmed]
  3. 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]
  4. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Legros, F., Lombès, A., Frachon, P., Rojo, M. Mol. Biol. Cell (2002) [Pubmed]
  5. Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Ishihara, N., Eura, Y., Mihara, K. J. Cell. Sci. (2004) [Pubmed]
  6. Control of mitochondrial morphology by a human mitofusin. Santel, A., Fuller, M.T. J. Cell. Sci. (2001) [Pubmed]
  7. 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]
  8. Molecular mechanism of mitochondrial membrane fusion. Griffin, E.E., Detmer, S.A., Chan, D.C. Biochim. Biophys. Acta (2006) [Pubmed]
  9. Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. Santel, A., Frank, S., Gaume, B., Herrler, M., Youle, R.J., Fuller, M.T. J. Cell. Sci. (2003) [Pubmed]
  10. Get the balance right: mitofusins roles in health and disease. Santel, A. Biochim. Biophys. Acta (2006) [Pubmed]
  11. What is the biological significance of the two mitofusin proteins present in the outer mitochondrial membrane of mammalian cells? Zorzano, A., Pich, S. IUBMB Life (2006) [Pubmed]
  12. Polymorphism, heteroplasmy, mitochondrial fusion and diabetes. Sato, A., Endo, H., Umetsu, K., Sone, H., Yanagisawa, Y., Saigusa, A., Aita, S., Kagawa, Y. Biosci. Rep. (2003) [Pubmed]
  13. Differences in mitochondrial movement and morphology in young and mature primary cortical neurons in culture. Chang, D.T., Reynolds, I.J. Neuroscience (2006) [Pubmed]
  14. 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]
 
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