Ugo1 and Mdm30 act sequentially during Fzo1-mediated mitochondrial outer membrane fusion

Anton, Fabian; Fres, Julia; Schauß, Astrid; Pinson, Benoı̂t; Praefcke, Gerrit J. K.; Langer, Thomas; Escobar-Henriques, Mafalda

doi:10.1242/jcs.073080

Cited by 80 publications

(100 citation statements)

References 67 publications

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“…Interestingly, Fzo is ubiquitinated by Mdm30, priming Fzo for degradation. The degradation is an essential step to achieve full fusion, likely by removing the DLP scaffold and leaving the membrane in an energetically unfavorable, highly bent state that relaxes upon fusion (Anton et al , 2011 ;Cohen et al , 2011 ). This is an interesting parallel to the observations reported for bacterial DynA.…”

Section: Mechanisms Of Membrane Fusion By Bacterial Dlpssupporting

confidence: 62%

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Structure and function of bacterial dynamin-like proteins

Bramkamp¹

2012

Biological Chemistry

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: Membrane dynamics are essential for numerous cellular processes in eukaryotic and prokaryotic cells. In eukaryotic cells, membrane fusion and fission are often catalyzed by large GTPases of the dynamin protein family. These proteins couple GTP hydrolysis to membrane deformation, which eventually leads to fusion or fission of the lipid bilayer. Mutations in eukaryotic dynamin-like proteins (DLPs) are associated with various diseases underscoring the importance to fully understand the biochemistry of these proteins. In recent years, a wealth of structural and biochemical data have been published that allow a detailed analysis of how dynamins or DLPs modulate biological membranes. However, less is known about the function of bacterial DLPs, although structural data exist. This review summarizes current knowledge about bacterial dynamins and discusses structural and functional properties in comparison to their eukaryotic counterparts.

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Section: Mechanisms Of Membrane Fusion By Bacterial Dlpssupporting

confidence: 62%

“…The yeast mitofusin Fzo1 shows G domain-dependent homodimerization. Upon further oligomerization, the outer membranes of the mitochondria are tied together, allowing membrane fusion (Anton et al , 2011 ;Cohen et al , 2011 ). Interestingly, Fzo is ubiquitinated by Mdm30, priming Fzo for degradation.…”

Section: Mechanisms Of Membrane Fusion By Bacterial Dlpsmentioning

confidence: 99%

Structure and function of bacterial dynamin-like proteins

Bramkamp¹

2012

Biological Chemistry

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“…Importantly, in the above experiments, we mated a rho + strain with a deleted DNM1 gene and containing the FZO1 gene under the control of an inducible GAL-promoter (P GAL ) with the HS rho − strain of WT background. The selection of the strains for this experiment was dictated by the following reasons: (1) deletion or repression of the FZO1 gene induces a very rapid destabilization of mitochondrial DNA in the wild-type background, while allowing preservation of full-length mtDNA in the Δdnm1 background (Bleazard et al, 1999); (2) according to the accepted model, the presence of Fzo1p on the outer membranes of the both mitochondria is required for their fusion (Anton et al, 2011); (3) in the background of our strain, transformation of P GAL promoter cassette in Δdnm1 HS rho − strain induces loss of mtDNA. Thus, to test the effect of FZO1, we repressed the gene only in one of the mating strains.…”

Section: Uncouplers Increase Percentages Of Rho + Diploid Progeny Of mentioning

confidence: 99%

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA

Karavaeva

Golyshev

Смирнова

et al. 2017

Journal of Cell Science

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Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8, ATG32 or ATG33, implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes.

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“…To facilitate mitochondrial outer membrane fusion, Fzo1 forms homodimers that tether two mitochondria. After GTP hydrolysis, Fzo1 is ubiquitinated by Mdm30 and then degraded following completion of outer membrane fusion (65,66). Similar to the mus-10 mutant of N. crassa, the mdm30 mutant also harbors fragmented mitochondria (64,67).…”

Section: Discussionmentioning

confidence: 98%

A uvs-5 Strain Is Deficient for a Mitofusin Gene Homologue, fzo1 , Involved in Maintenance of Long Life Span in Neurospora crassa

et al. 2013

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Mitochondria are highly dynamic organelles that continuously fuse and divide. To maintain mitochondria, cells establish an equilibrium of fusion and fission events, which are mediated by dynamin-like GTPases. We previously showed that an mus-10 strain, a mutagen-sensitive strain of the filamentous fungus Neurospora crassa, is defective in an F-box protein that is essential for the maintenance of mitochondrial DNA (mtDNA), long life span, and mitochondrial morphology. Similarly, a uvs-5 mutant accumulates deletions within its mtDNA, has a shortened life span, and harbors fragmented mitochondria, the latter of which is indicative of an imbalance between mitochondrial fission and fusion. Since the uvs-5 mutation maps very close to the locus of fzo1, encoding a mitofusin homologue thought to mediate mitochondrial outer membrane fusion, we determined the sequence of the fzo1 gene in the uvs-5 mutant. A single amino acid substitution (Q368R) was found in the GTPase domain of the FZO1 protein. Expression of wild-type FZO1 in the uvs-5 strain rescued the mutant phenotypes, while expression of a mutant FZO1 protein did not. Moreover, when knock-in of the Q368R mutation was performed on a wild-type strain, the resulting mutant displayed phenotypes identical to those of the uvs-5 mutant. Therefore, we concluded that the previously unidentified uvs-5 gene is fzo1. Furthermore, we used immunoprecipitation analysis to show that the FZO1 protein interacts with MUS-10, which suggests that these two proteins may function together to maintain mitochondrial morphology.

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Ugo1 and Mdm30 act sequentially during Fzo1-mediated mitochondrial outer membrane fusion

Cited by 80 publications

References 67 publications

Structure and function of bacterial dynamin-like proteins

Structure and function of bacterial dynamin-like proteins

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA

A uvs-5 Strain Is Deficient for a Mitofusin Gene Homologue, fzo1 , Involved in Maintenance of Long Life Span in Neurospora crassa

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