| 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
|
| Resource |
| C.elegans |
tm1826
tm469
tm459
tm2214
tm2108
tm2100
tm3124
tm2166
tm2024
tm2139
tm1990
tm2078
tm2159
tm2059
tm2111 |
