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FZO1  -  mitofusin

Saccharomyces cerevisiae S288c

Synonyms: Mitofusin FZO1, Transmembrane GTPase FZO1, YBR1241, YBR179C
 
 
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High impact information on FZO1

  • A central component of the mitochondrial fusion apparatus is the conserved GTPase Fzo1 in the outer membrane of mitochondria [1].
  • During vegetative growth, Mdm30 mediates ubiquitylation of Fzo1 and degradation of the mitofusin in an ubiquitin-proteasome-dependent process [2].
  • Regulation of mitochondrial fusion by the F-box protein Mdm30 involves proteasome-independent turnover of Fzo1 [3].
  • This contrasts to the ubiquitin- and proteasome-dependent turnover of Fzo1 in alpha-factor-arrested yeast cells [3].
  • Interestingly, mutations in a second mitochondrial-associated dynamin-related GTPase, Mgm1p, produce similar phenotypes to fzo1 and ugo cells [4].
  • Mitochondrial fusion requires two integral outer membrane components, Fzo1p and Ugo1p [4].
 

Biological context of FZO1

  • This mgm1 phenotype is identical to that observed in cells with a conditional mutation in FZO1, which encodes a transmembrane GTPase required for mitochondrial fusion, raising the possibility that Mgm1p is also required for fusion [5].
  • Point mutations that alter conserved residues in the GTPase domain do not affect Fzo1p localization but disrupt mitochondrial fusion [1].
  • Fzo1p is a novel component required for the biogenesis of functional mitochondria in the yeast Saccharomyces cerevisiae [6].
  • In response to a G1 arrest evoked by the mating pheromone alpha factor the mitochondrial network fragmented into small pieces, which was accompanied by dramatic down-regulation of Fzo1 [7].
 

Anatomical context of FZO1

  • Taken together, these data suggest a model where Mgm1p functions in fusion to remodel the inner membrane and to connect the inner membrane to the outer membrane via its interactions with Ugo1p and Fzo1p, thereby helping to coordinate the behavior of the four mitochondrial membranes during fusion [4].
  • Connection of the mitochondrial outer and inner membranes by Fzo1 is critical for organellar fusion [8].
  • A conditional fzo1 mutation causes the mitochondrial reticulum to fragment and blocks mitochondrial fusion during yeast mating [1].
  • Fzo1p is an integral protein of the mitochondrial outer membrane exposing its major part to the cytosol [6].
 

Associations of FZO1 with chemical compounds

  • Additionally, each of the gag mutations prevented mitochondrial fragmentation caused by loss of the mitochondrial fusion factor, Fzo1p, or by treatment of cells with sodium azide [9].
  • Homotypic trans interactions of the ancient outer transmembrane guanosine triphosphatase, Fzo1, were required to promote the fusion of mitochondrial outer membranes, whereas electrical potential was also required for fusion of inner membranes [10].
 

Physical interactions of FZO1

  • Here, we show that the cytoplasmic domain of Ugo1p directly interacts with Fzo1p, whereas its intermembrane space domain binds to Mgm1p [11].
 

Regulatory relationships of FZO1

  • Our results raise the possibility that Mgm1p regulates fusion of the mitochondrial outer membrane through its interactions with Fzo1p and Ugo1p [12].
  • Our results suggest that Mdm30 controls mitochondrial shape by regulating the steady-state level of Fzo1 and point to a connection of the ubiquitin/26S proteasome system and mitochondria [13].
  • Although a role for the F-box protein Mdm30 in regulating the stability of Fzo1 has been proposed, the molecular basis for the regulation of the fission to fusion ratio of mitochondria remains unknown [7].
 

Other interactions of FZO1

  • In Saccharomyces cerevisiae, mitochondrial fusion requires at least two outer membrane proteins, Fzo1p and Ugo1p [12].
  • However, in contrast to fzo1 cells, deletion of DNM1 in mgm1 cells restores mitochondrial fusion during mating [5].
  • However, deletion of MDM30 did not stabilize Fzo1 after mating pheromone treatment, showing a different mechanism from the previously reported process of steady state Fzo1 regulation [7].

 

References

  1. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. Hermann, G.J., Thatcher, J.W., Mills, J.P., Hales, K.G., Fuller, M.T., Nunnari, J., Shaw, J.M. J. Cell Biol. (1998) [Pubmed]
  2. Ubiquitin-proteasome-dependent degradation of a mitofusin, a critical regulator of mitochondrial fusion. Cohen, M.M., Leboucher, G.P., Livnat-Levanon, N., Glickman, M.H., Weissman, A.M. Mol. Biol. Cell. (2008) [Pubmed]
  3. Regulation of mitochondrial fusion by the F-box protein Mdm30 involves proteasome-independent turnover of Fzo1. Escobar-Henriques, M., Westermann, B., Langer, T. J. Cell Biol. (2006) [Pubmed]
  4. The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion. Wong, E.D., Wagner, J.A., Scott, S.V., Okreglak, V., Holewinske, T.J., Cassidy-Stone, A., Nunnari, J. J. Cell Biol. (2003) [Pubmed]
  5. The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. Wong, E.D., Wagner, J.A., Gorsich, S.W., McCaffery, J.M., Shaw, J.M., Nunnari, J. J. Cell Biol. (2000) [Pubmed]
  6. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. Rapaport, D., Brunner, M., Neupert, W., Westermann, B. J. Biol. Chem. (1998) [Pubmed]
  7. Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae. Neutzner, A., Youle, R.J. J. Biol. Chem. (2005) [Pubmed]
  8. Connection of the mitochondrial outer and inner membranes by Fzo1 is critical for organellar fusion. Fritz, S., Rapaport, D., Klanner, E., Neupert, W., Westermann, B. J. Cell Biol. (2001) [Pubmed]
  9. Gag3p, an outer membrane protein required for fission of mitochondrial tubules. Fekkes, P., Shepard, K.A., Yaffe, M.P. J. Cell Biol. (2000) [Pubmed]
  10. Mitochondrial fusion intermediates revealed in vitro. Meeusen, S., McCaffery, J.M., Nunnari, J. Science (2004) [Pubmed]
  11. Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. Sesaki, H., Jensen, R.E. J. Biol. Chem. (2004) [Pubmed]
  12. Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial outer membrane. Sesaki, H., Southard, S.M., Yaffe, M.P., Jensen, R.E. Mol. Biol. Cell (2003) [Pubmed]
  13. Mdm30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast. Fritz, S., Weinbach, N., Westermann, B. Mol. Biol. Cell (2003) [Pubmed]
 
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