論文 - 詳細
| RRC ID | 88153 |
|---|---|
| 著者 | Obinata H, Watanabe T, Takahashi H, Shimo S, Oda T, Sugimoto A, Niwa S. |
| タイトル | SLC-25A46 regulates mitochondrial fusion through the mitofusin protein FZO-1 and is essential for maintaining neuronal morphology. |
| ジャーナル | J Cell Sci |
| Abstract |
Mitochondria are dynamic organelles shaped by sequential fission and fusion events. The mitochondrial protein SLC25A46 has been identified as a causative gene for mitochondrial neuropathies. However, the function of SLC25A46 in mitochondrial morphogenesis remains controversial, with several reports suggesting it acts as a mitochondrial fission factor, whereas others propose it as a fusion factor. In this study, employing forward genetics, we identified slc-25A46, a Caenorhabditis elegans ortholog of human SLC25A46, as an essential factor for mitochondrial fusion. Suppressor mutagenesis screening revealed loss-of-function mutations in drp-1, a mitochondrial fission factor, as suppressors of slc-25A46. The phenotype of slc-25A46 mutants is similar to that of mutants in the worm mitofusin ortholog fzo-1, wherein the mitochondrial fusion factor is disrupted. Overexpressing FZO-1 mitigated mitochondrial defects in slc-25a46 mutants, indicating that SLC-25A46 promotes fusion through FZO-1. Disease model worms carrying mutations associated with SLC25A46 exhibited mitochondrial fragmentation and accelerated neurodegeneration, suggesting that slc-25A46 maintains neuronal morphology through regulating mitochondrial fusion regulation. |
| 巻・号 | 138(12) |
| 公開日 | 2025-6-15 |
| DOI | 10.1242/jcs.263571 |
| PII | 368363 |
| PMID | 40444356 |
| PMC | PMC12273626 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism GTP Phosphohydrolases Humans Membrane Proteins* / genetics Membrane Proteins* / metabolism Mitochondria* / genetics Mitochondria* / metabolism Mitochondrial Dynamics* / genetics Mitochondrial Proteins* / genetics Mitochondrial Proteins* / metabolism Mutation / genetics Neurons* / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1108 tm1133 tm1107 |