Reference - Detail
| RRC ID | 84177 |
|---|---|
| Author | Ko SH, Cho KA, Li X, Ran Q, Liu Z, Chen L. |
| Title | GPX modulation promotes regenerative axonal fusion and functional recovery after injury through PSR-1 condensation. |
| Journal | Nat Commun |
| Abstract |
Axonal fusion represents an efficient way to recover function after nerve injury. However, how axonal fusion is induced and regulated remains largely unknown. We discover that ferroptosis signaling can promote axonal fusion and functional recovery in C. elegans in a dose-sensitive manner. Ferroptosis-induced lipid peroxidation enhances injury-triggered phosphatidylserine exposure (PS) to promote axonal fusion through PS receptor (PSR-1) and EFF-1 fusogen. Axon injury induces PSR-1 condensate formation and disruption of PSR-1 condensation inhibits axonal fusion. Extending these findings to mammalian nerve repair, we show that loss of Glutathione peroxidase 4 (GPX4), a crucial suppressor of ferroptosis, promotes functional recovery after sciatic nerve injury. Applying ferroptosis inducers to mouse sciatic nerves retains nerve innervation and significantly enhances functional restoration after nerve transection and resuture without affecting axon regeneration. Our study reveals an evolutionarily conserved function of lipid peroxidation in promoting axonal fusion, providing insights for developing therapeutic strategies for nerve injury. |
| Volume | 16(1) |
| Pages | 1079 |
| Published | 2025-1-27 |
| DOI | 10.1038/s41467-025-56382-z |
| PII | 10.1038/s41467-025-56382-z |
| PMID | 39870634 |
| PMC | PMC11772683 |
| MeSH | Animals Axons* / metabolism Axons* / physiology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Ferroptosis Lipid Peroxidation Mice Nerve Regeneration* / physiology Peripheral Nerve Injuries Phosphatidylserines / metabolism Phospholipid Hydroperoxide Glutathione Peroxidase* / genetics Phospholipid Hydroperoxide Glutathione Peroxidase* / metabolism Recovery of Function / physiology Sciatic Nerve / injuries Sciatic Nerve / metabolism |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Bluesky |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| C.elegans | tm1826 tm469 tm459 tm2214 tm2108 tm2100 tm3124 tm2166 tm2024 tm2139 tm1990 tm2078 tm2159 tm2059 tm2111 |