Developmentally Regulated Mitochondrial Fusion Mediated by a Conserved, Novel, Predicted GTPase
Open accessAbstract
The Drosophila melanogaster fuzzy onions (fzo) gene encodes the first known protein mediator of mitochondrial fusion. During Drosophila spermatogenesis, mitochondria in early postmeiotic spermatids aggregate, fuse, and elongate beside the growing flagellar axoneme. fzo mutant males are defective in this developmentally regulated mitochondrial fusion and are sterile. fzo encodes a large, novel, predicted transmembrane GTPase that becomes detectable on spermatid mitochondria late in meiosis II, just prior to fusion, and disappears soon after fusion is complete. Missense mutations that alter conserved residues required for GTP binding in other GTPases inhibit the fusogenic activity of Fzo in vivo but do not affect its localization. Fzo has homologs of unknown function in mammals, nematodes, and yeast.
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Mfn2 is a nuclear-encoded mitochondrial protein that is highly expressed in skeletal muscle, heart, and brain.
“Mfn2 is a nuclear-encoded mitochondrial protein that shows homology with Drosophila or yeast Fzo proteins (26,27) and is highly expressed in skeletal muscle, the heart, and the brain (23).”
From Expression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [26]
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- Authors
- Hales, K. G., & Fuller, M. T.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Fuller, Margaret T
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-07
- Volume
- 90
- Issue
- 1
- Pages
- 121-129
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2147207574
- Cited by
- 611
- References
- 52
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 21 · 2023: 20 · 2022: 17 · 2021: 22 · 2020: 21 · 2019: 16 · 2018: 24 · 2017: 20 · 2016: 24 · 2015: 19 · 2014: 17 · 2013: 17 · 2012: 39
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd029194-05)
- National Human Genome Research Institute (HG00044)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (1RO1-HD29194)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial fusion, GTPase, spermatogenesis, meiosis II, male sterility, GTP binding, Drosophila melanogaster, mitochondrial elongation
- MeSH terms
- Amino Acid Sequence, Animals, Chromosome Mapping, Drosophila melanogaster, Female, Genes, Recessive, Humans, Infertility, Male, Intracellular Membranes, Male, Membrane Fusion, Membrane Proteins, Mitochondria, Molecular Sequence Data, Polymorphism, Genetic, Recombination, Genetic, Spermatids, Mutagenesis, Sequence Alignment, Conserved Sequence, Genes, Insect, Sequence Homology, Amino Acid, GTP Phosphohydrolases, Drosophila Proteins, Animals, Genetically Modified
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