FZO1 mitofusin [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: FZO1
Official Full Name: mitofusin
Primary source: SGD:S000000383
Locus tag: YBR179C
See related: AllianceGenome:SGD:S000000383; FungiDB:YBR179C; VEuPathDB:YBR179C
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Summary: Enables GTPase activity and peroxisome-mitochondrion membrane tether activity. Involved in mitochondrial fusion. Acts upstream of or within intracellular distribution of mitochondria. Located in mitochondrial outer membrane. Is active in peroxisomal-mitochondrial contact site and peroxisome. Used to study Charcot-Marie-Tooth disease type 2A2A and Charcot-Marie-Tooth disease type 2A2B. Human ortholog(s) of this gene implicated in Charcot-Marie-Tooth disease; Charcot-Marie-Tooth disease type 2A2A; Charcot-Marie-Tooth disease type 2A2B; Charcot-Marie-Tooth disease type 6; and multiple symmetric lipomatosis. Orthologous to human MFN1 (mitofusin 1) and MFN2 (mitofusin 2). [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

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See FZO1 in Genome Data Viewer

Location:: chromosome: II

Exon count:: 1

Sequence:: Chromosome: II; NC_001134.8 (586547..589114, complement)

Chromosome II - NC_001134.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001134.8

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

E4 ubiquitin ligase promotes mitofusin turnover and mitochondrial stress response.
Title: E4 ubiquitin ligase promotes mitofusin turnover and mitochondrial stress response.
Cdc48 did not affect the ubiquitylated but fusion-incompetent variants, indicating that Fzo1 ubiquitylation is only controlled after membrane merging. Authors present an integrated model on how mitochondrial outer membranes fuse, a critical process for their respiratory function.
Title: Plasticity in salt bridge allows fusion-competent ubiquitylation of mitofusins and Cdc48 recognition.
Physics-based oligomeric models of the yeast mitofusin Fzo1 at the molecular scale in the context of membrane docking.
Title: Physics-based oligomeric models of the yeast mitofusin Fzo1 at the molecular scale in the context of membrane docking.
Here, the authors identify a new function of Cdc48 in ubiquitin-dependent regulation of mitochondrial dynamics. Cdc48 synergistically regulates the ubiquitylation status of Fzo1 via Ubp12 and Ubp2, allowing to control the balance between activation or repression of mitochondrial fusion.
Title: Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion.
The predicted architecture of Fzo1 improves upon the current domain annotation, with a precise description of the helical spans linked by flexible hinges, which are likely of functional significance. Site-directed mutagenesis validates salient aspects of this model, notably, the long-distance contacts and residues participating in hinges. GDP is predicted to interact with Fzo1 via G1 and G4 motifs of the GTPase domain.
Title: A membrane-inserted structural model of the yeast mitofusin Fzo1.
The Saccharomyces cerevisiae Fzo1 and animal Mitofusin proteins are highly diverged from one another and lack strong sequence similarity.
Title: A new mitofusin topology places the redox-regulated C terminus in the mitochondrial intermembrane space.
Mdm30-Ubp2-Rsp5 crosstalk regulates mitochondrial fusion by coordinating an intricate balance between Fzo1 turnover and the status of fatty acids saturation.
Title: An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion.
The results indicated that two different Ubp3 and Ubx2 complexes independently regulate mitochondrial fusion and Fzo1 turnover.
Title: Two Cdc48 cofactors Ubp3 and Ubx2 regulate mitochondrial morphology and protein turnover.
Findings suggest a sequence of events in early mitochondrial fusion where Fzo1 GTPase-domain-dependent tethering leads to recruitment of SCF(Mdm30) and ubiquitin-mediated degradation of Fzo1, which facilitates mitochondrial fusion.
Title: Sequential requirements for the GTPase domain of the mitofusin Fzo1 and the ubiquitin ligase SCFMdm30 in mitochondrial outer membrane fusion.
Fzo1 assembles into homo-dimers, depending on Ugo1 and on GTP binding to Fzo1.
Title: Ugo1 and Mdm30 act sequentially during Fzo1-mediated mitochondrial outer membrane fusion.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables GTP binding	IEA Inferred from Electronic Annotation more info
enables GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activity	IEA Inferred from Electronic Annotation more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables membrane scission GTPase motor activity	IEA Inferred from Electronic Annotation more info
enables peroxisome-mitochondrion membrane tether activity	IDA Inferred from Direct Assay more info	PubMed
enables peroxisome-mitochondrion membrane tether activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within intracellular distribution of mitochondria	IGI Inferred from Genetic Interaction more info	PubMed
involved_in mitochondrial fusion	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial fusion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial fusion	IPI Inferred from Physical Interaction more info	PubMed
involved_in mitochondrion localization	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrion organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in mitochondrial outer membrane	HDA more info	PubMed
is_active_in mitochondrial outer membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial outer membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
is_active_in peroxisomal-mitochondrial contact site	IDA Inferred from Direct Assay more info	PubMed
is_active_in peroxisome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mitofusin

NP_009738.1

Mitofusin, involved in mitochondrial outer membrane fusion; mediates contacts between mitochondria and peroxisomes that regulate mitochondrial fusion; GTPase domain is required for auto-oligomerization and for efficient tethering, homotypic fusion and degradation of Fzo1p; role in mitochondrial genome maintenance; targeted for destruction by SCF-Mdm30p and the cytosolic ubiquitin-proteasome system; activity regulated by ubiquitination at conserved lysines and by deubiquitinases Ubp2p and Ubp12p

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_001134.8 Reference assembly

Range

586547..589114 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001178527.1 → NP_009738.1 TPA: mitofusin [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_009738.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VQH3, P38297

UniProtKB/TrEMBL

B3LMY2, C7GUJ2, G2W9I0, N1P8C8

Conserved Domains (1) summary

COG0699
Location:128 → 841

CrfC; Replication fork clamp-binding protein CrfC (dynamin-like GTPase family) [Replication, recombination and repair]