Peer-reviewedCC BYRedox biology
NEURL1-mediated K63-ubiquitination of SLC40A1 drives ferroptosis resistance in pathological scars: Therapeutic targeting via autophagy-activating microneedles.
5 affiliations
- 1Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China.
- 2Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
- 3Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
- 4Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China. Electronic address: [email protected].
- 5Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. Electronic address: [email protected].
Abstract
Ferroptosis resistance contributes to pathological skin scarring, but the underlying regulatory mechanisms remain unclear. Here, we identified a novel selective autophagy pathway NEURL1-SQSTM1/p62-SLC40A1 that controls fibroblast ferroptosis and scar formation. SLC40A1 is upregulated in human scars, conferring ferroptosis resistance by promoting iron efflux. Mechanistically, NEURL1 mediates K63-linked ubiquitination of SLC40A1, enabling its recognition by SQSTM1 for lysosomal degradation. A microneedle system co-delivering curcumin (autophagy activator) and siSLC40A1 effectively activates this axis, induces ferroptosis, and alleviates scarring in vivo. Our findings reveal a new therapeutic target and strategy for pathological scars.
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BibTeX
@article{lv2026neurl1mediated,
title = {{NEURL1-mediated K63-ubiquitination of SLC40A1 drives ferroptosis resistance in pathological scars: Therapeutic targeting via autophagy-activating microneedles.}},
author = {Mengzhu Lv and Jiamei Liu and Qi Dong and Zibo Guo and Qianlong Wu and Simeng Zhang and Shengye Liu},
journal = {Redox biology},
year = {2026},
month = sep,
doi = {10.1016/j.redox.2026.104420},
url = {https://europepmc.org/article/MED/42858534},
note = {CC BY},
}
RIS
TY - JOUR
TI - NEURL1-mediated K63-ubiquitination of SLC40A1 drives ferroptosis resistance in pathological scars: Therapeutic targeting via autophagy-activating microneedles.
AU - Mengzhu Lv
AU - Jiamei Liu
AU - Qi Dong
AU - Zibo Guo
AU - Qianlong Wu
AU - Simeng Zhang
AU - Shengye Liu
PY - 2026
DA - 2026/09/29
JO - Redox biology
DO - 10.1016/j.redox.2026.104420
UR - https://europepmc.org/article/MED/42858534
AB - Ferroptosis resistance contributes to pathological skin scarring, but the underlying regulatory mechanisms remain unclear. Here, we identified a novel selective autophagy pathway NEURL1-SQSTM1/p62-SLC40A1 that controls fibroblast ferroptosis and scar formation. SLC40A1 is upregulated in human scars, conferring ferroptosis resistance by promoting iron efflux. Mechanistically, NEURL1 mediates K63-linked ubiquitination of SLC40A1, enabling its recognition by SQSTM1 for lysosomal degradation. A microneedle system co-delivering curcumin (autophagy activator) and siSLC40A1 effectively activates this axis, induces ferroptosis, and alleviates scarring in vivo. Our findings reveal a new therapeutic target and strategy for pathological scars.
SN - 2213-2317
ER -