Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 43 min ago
Peer-reviewedCC BYJournal of cellular and molecular medicine

Knockdown of Smurf1 Promotes Autophagy-Dependent Ferroptosis in Acute Liver Failure by Inhibiting Ubiquitin-Mediated Ulk1 Degradation.

  • Pei Shi1
  • Mengyu Tao1
  • Yuyu Zeng1
  • Yuchen Peng1
  • Xiaoping Wu1
  1. 1Department of Infectious Diseases, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Read full textPDFDOICite

Abstract

Treating acute liver failure (ALF) relies on rescuing dying hepatocytes and restoring liver regeneration. Ferroptosis contributes to ALF development, so regulating iron homeostasis or lipid peroxide production may be an effective treatment strategy. Ubiquitination can modify ferroptosis and is involved in liver diseases. The study aims to explore the mechanism of E3 ubiquitin ligase Smurf1 regulating ferroptosis in acute liver failure. Screened using proteomics, bioinformatics and experimental verification, we identified Smurf1, a ubiquitin-related protein associated with ferroptosis. Functional experiments were used to verify that Smurf1 regulates hepatocyte ferroptosis and acute liver failure. Furthermore, ubiquitination assays, western blotting and Co-IP experiments were applied to identify Ulk1 as a substrate of Smurf1. Further, we constructed the cell and animal models with silencing or overexpression of Smurf1 and Ulk1 to clarify the potential mechanism of Smurf1 on ferroptosis in ALF. Knockdown or overexpression of Smurf1 promoted or inhibited hepatocyte ferroptosis, respectively. In the animal model, knockdown of Smurf1 significantly aggravated the progression of ALF, suggesting that Smurf1 knockdown exacerbated liver failure by promoting hepatocyte ferroptosis. In conclusion, Smurf1 interacted with the new substrate Ulk1 and promoted its ubiquitin-mediated degradation at the post-translational level, and Smurf1 knockdown promotes ferroptosis in hepatocytes in a manner dependent on Ulk1-mediated autophagy activation.

Related

  1. Proteasome Inhibitor MG132 Facilitates Antiviral Effects by Inhibiting TFEB Degradation and Activating Autophagy
    Naiyu Liu, Yingrui Wei, Shanshan Fu +2
    ACS OmegaPeer-reviewedCC BY-NC-ND 4.0Full textEpidemiology & public healthCrossref
  2. NEDD9 confers ferroptosis resistance in liver cancer by inhibiting autophagy via the AKT‑mTOR signaling pathway
    Qisheng He, Yu Bai, Xiaojing Xu +5
    Biology DirectPeer-reviewedCC BY-NC-ND 4.0Full textOncologyPMC
  3. UCHL5 stabilizes ALK5 to promote autophagy dependent ferroptosis in osteoarthritis
    Rilong Jin, Chen Li, Mingfeng Xiong +1
    Communications BiologyPeer-reviewedCC BY 4.0Full textGeneral medicineCrossref
  4. The dual role of autophagy in gynecologic malignancies: promoting and inhibiting
    Dongying Gai, Ning Jia, Fanghua Qi +4
    Frontiers in cell and developmental biologyPeer-reviewedCC BYFull textEpidemiology & public healthEurope PMCEurope PMCPMC
  5. SGLT2i protects against myocardial I/R-induced coronary microvascular injury by inhibiting glycocalyx degradation
    Xiaoru Huang, Yunqi Jiang, Xinye Xu +2
    BMC MedicinePeer-reviewedCC BY 4.0General medicineCrossref

Cite

BibTeXRIS
BibTeX
@article{shi2026knockdown,
  title = {{Knockdown of Smurf1 Promotes Autophagy-Dependent Ferroptosis in Acute Liver Failure by Inhibiting Ubiquitin-Mediated Ulk1 Degradation.}},
  author = {Pei Shi and Mengyu Tao and Yuyu Zeng and Yuchen Peng and Xiaoping Wu},
  journal = {Journal of cellular and molecular medicine},
  year = {2026},
  month = oct,
  doi = {10.1111/jcmm.71405},
  url = {https://europepmc.org/article/MED/42957609},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Knockdown of Smurf1 Promotes Autophagy-Dependent Ferroptosis in Acute Liver Failure by Inhibiting Ubiquitin-Mediated Ulk1 Degradation.
AU  - Pei Shi
AU  - Mengyu Tao
AU  - Yuyu Zeng
AU  - Yuchen Peng
AU  - Xiaoping Wu
PY  - 2026
DA  - 2026/10/29
JO  - Journal of cellular and molecular medicine
DO  - 10.1111/jcmm.71405
UR  - https://europepmc.org/article/MED/42957609
AB  - Treating acute liver failure (ALF) relies on rescuing dying hepatocytes and restoring liver regeneration. Ferroptosis contributes to ALF development, so regulating iron homeostasis or lipid peroxide production may be an effective treatment strategy. Ubiquitination can modify ferroptosis and is involved in liver diseases. The study aims to explore the mechanism of E3 ubiquitin ligase Smurf1 regulating ferroptosis in acute liver failure. Screened using proteomics, bioinformatics and experimental verification, we identified Smurf1, a ubiquitin-related protein associated with ferroptosis. Functional experiments were used to verify that Smurf1 regulates hepatocyte ferroptosis and acute liver failure. Furthermore, ubiquitination assays, western blotting and Co-IP experiments were applied to identify Ulk1 as a substrate of Smurf1. Further, we constructed the cell and animal models with silencing or overexpression of Smurf1 and Ulk1 to clarify the potential mechanism of Smurf1 on ferroptosis in ALF. Knockdown or overexpression of Smurf1 promoted or inhibited hepatocyte ferroptosis, respectively. In the animal model, knockdown of Smurf1 significantly aggravated the progression of ALF, suggesting that Smurf1 knockdown exacerbated liver failure by promoting hepatocyte ferroptosis. In conclusion, Smurf1 interacted with the new substrate Ulk1 and promoted its ubiquitin-mediated degradation at the post-translational level, and Smurf1 knockdown promotes ferroptosis in hepatocytes in a manner dependent on Ulk1-mediated autophagy activation.
SN  - 1582-1838
SN  - 1582-4934
ER  -